Main model organisms for Homo sapiens (genome sequencing projects)

• vivisection : the performance of surgical procedures upon living animals for purposes of research.

• Germany : > 2.126 million animals were used for research in 2001, Of the total, some 1.024 million were mice, 512,393 rats, 303,590 fishes, 117,890 rabbits, and 63,665 birds. Among larger animals, some 11,661 pigs, 2,402 cattle, 4,430 dogs, and 648 cats were used.
• UK animal experiments :


• 2.73 million experiments in the 12 months of 2002
• total number of procedures rose by 4.2% on 2001
• usage :
• research and drug development (80%)
• safety testing (18%)

• Deuterostomia; Chordata; Craniata
• Vertebrata (vertebrates); Gnathostomata; Teleostomi; Euteleostomi; Sarcopterygii; Tetrapoda; Amniota; Mammalia; Theria; Eutheria; Euarchontoglires;
• Primates; Simiiformes
• Catarrhini
• Cercopithecoidea; Cercopithecidae; Cercopithecinae
• Macaca
• Macaca mulatta (a.k.a. rhesus monkey) : the Indian-origin rhesus, has been the favored nonhuman primate in biomedical research for about 50 years, since the polio pandemic. Information on the biology of the species is the broadest of any primate other than the human But in the late 1970s, India, a major supplier, banned export of the animals as a conservation measure. Still, because of their popularity and because of the amount of information about them, researchers have grown accustomed to using Indian rhesus monkeys, even though there are rhesus monkeys available from China, for example. With the law of supply and demand working smoothly, prices for rhesus monkeys have shot up. Where a few years ago you might have paid $2000 for a rhesus monkey, now the price can be anywhere from 5000 to $12,000. See also transmissible and nontrasmissible diseases carried by rhesus monkey.


There is abundant evidence of harm to humans as a result of experiments on primates. Such evidence includes:
• primates' track record at predicting drugs' dangerous side effects is abysmal.
• many drugs that were safe for primates have gone on to injure and kill people. For example, amrinone (for heart failure) was tested on numerous non-human primates and released with confidence. However, one in five human patients haemorrhaged as the drug prevented normal blood clotting.
• an Alzheimer's vaccine was withdrawn in 2001 when it caused serious brain inflammation in patients, after proving safe and effective in tests on monkeys.
• countless drugs for stroke have been developed and tested in primates and other animals, yet all of them have failed and even harmed patients in clinical trials.
• monkeys do not suffer from Alzheimer's disease, Parkinson's disease or Huntington's disease and when these diseases are artificially induced they manifest very differently from the real human versions.
• human brains can now be studied non-invasively using remarkable high-tech scanners. These enable the conscious brain to be observed while engaged in a variety of cognitive tasks (talking, singing, reading, writing, etc) of which monkeys are not even capable - and thus clearly could not provide any relevant insight.
Experimenting on monkeys in the hope of unlocking the secrets of the human brain is an exercise in futility. The most dramatic differences between humans and other primates are in the brain. Our brain is 4 times larger than that of a chimpanzee, which is 4 times larger than that of a macaque. Biochemical pathways in the human brain are unique. Gene expression in our brain is dramatically different from that of the chimpanzee. Future advances in our understanding and treatment of neurodegenerative diseases will come from where they always have - human-based observation and ethical clinical research. Everything we know about these diseases has been learned from autopsies of patients, population research and studies using human tissues cultured from biopsies or autopsies. Today, medicine is focused on variation between individual people at the level of SNPs. This is where the clues to diseases and their treatments will be found - not in artificially induced versions of the disease in an entirely separate species. The funding for the primate centre would be better spent on more scientifically modern and reliable research methods involving DNA microarrays; bioinformatics; microdosing with subsequent PET analysis; human stem cells; large clinical studies and so on.

Rhesus macaques will pay to look at images of powerful or sexually interesting fellows : monkeys will make sacrifices to gain socially useful information, much as a human might spend money on a newspaper. Male monkeys will 'pay' in fruit juice to look at a picture of a socially dominant monkey or a female's hindquarters. In the wild, the animals help their fitness by monitoring what their leaders are doing, and which females are sexually receptive. The researchers gave captive male rhesus macaques 2 options: a drink of cherry juice, or a different-sized shot of juice and the chance to look at one of a range of pictures of their troop members for just over half a second. By varying the amounts of juice, the team worked out how much the monkeys valued each image. Monkeys would take a juice cut to look at powerful males' faces or the perineum of a female^ref. But to persuade the monkeys to stare at subordinate males, the researchers had to bribe them with larger drinks. Gathering social information has costs as well as benefits : if you stare at someone too long they might attack you. This goes for humans too: think about how uncomfortable it is to be stared at by a stranger for any length of time. No surprise, then, that the juice-to-picture exchange rate was highest for images of female rears. This is not monkey pornography : it's more to do with assessing sexual receptiveness, which in the wild also involves females' behaviour and smell. The monkeys do not necessarily know they are looking at a picture, so their behaviour is consistent with what they might do in a face-to-face situation. Human autistics are not motivated to look at other people, and are poor at gathering emotional information when they do. The monkey study might even help to explain humans' fascination with gossip magazine. The urge to keep tabs on sexy, powerful people may stem from our tribal past, when the actions of the group's movers and shakers would have influenced our own lives.
• Papio spp. (baboons) are an old world monkey that on an evolutionary scale is more closely related to the hominoid primates, including humans.  The baboon also has a number of advantages over other old world monkey species that have been more commonly used in research investigations.  The baboons share a number of immunologic and physiologic characteristics that closely resemble humans.  A number of studies have been performed to examine various aspects of the baboon as a model for infectious diseases and in immunologic assessments.  In particular, the baboon represents a relevant and highly predictive animal model for investigations into vaccine safety and immunogenicity.  An overview of studies that have utilized the baboon and other nonhuman primate species as models to assess plasmid DNA immunization with regards to safety and immunogenicity provides insight into how these strategies will potential impact human health as potential vaccines.
• Hominoidea; Hominidae; Homo/Pan/Gorilla group; Pan
• Pan troglodytes (a.k.a. chimpanzee) : an anthropoid ape that inhabits the tropical rain forests of Africa and is used for experimental purposes because of its susceptibility to some human diseases and in behavioral studies because of its high level of intelligence.


Chimps can not only use tools, but also seem to follow the fashion in how they are used. Researchers have found that a group of chimpanzees will stick to the same method used by their peers, even if they stumble across a different way of using a tool by themselves^ref. That shows that chimps follow a cultural norm that is socially learned and maintained - proof, perhaps, that chimpanzees really do have culture. Chimpanzees are known to have many complex behaviours, including tool use and grooming, that place them second only to humans. Scientists have long assumed that chimpanzee populations maintain such traditions the same way humans do: by learning to imitate each other.  But proof for social learning in wild chimpanzees has been hard to come by. One problem is that simply observing one animal watching another doesn't prove that he is learning a behaviour. If he picks up the same tricks, it could be that he learned them by himself. The solution is to check whether chimpanzees can start and maintain a cultural tradition in a controlled environment. To do this, he and his colleagues used chimpanzees kept at the Yerkes Primate Center for Advanced Study of Ape and Human Evolution at Emory University in Atlanta, Georgia. The researchers placed a grape on a platform inside a box, with an obstructing block to stop it falling out. They then taught two different chimpanzees two different ways to use a stick to get the grape. One used the stick to lift the block out of the box, allowing the grape to fall out. The other learned to poke the block backwards, pushing the grape off the back of the platform and again allowing it to fall out. Once trained, the animals were returned to their social groups. As expected, most of the peers used the same technique as the one they observed from the trained chimp. Animals that didn't have an example to follow simply couldn't get the grape out. Some animals did spontaneously switch from one behaviour to the other when they tried to retrieve the grape, figuring out the alternative method themselves. But two months later, most animals had switched back to the majority behaviour in their group. Whiten points out that even animals who initially poked - a behavior more natural for chimpanzees than lifting - reverted to lifting eventually. "This is an even stronger social learning tendency than we went out to test for. This is narrowing the gap between humans and non-humans. It is the first proof that animals pick up a tradition by imitation. But te chimps might have learned how to get the grape by watching how the boxes themselves work, rather than by watching other chimps. But does this show that chimpanzees have 'culture'? Some experts think so. But the study doesn't provides sufficient proof to call chimpanzee traditions by that name. Besides, the most interesting thing is to investigate how chimp and human behaviours are alike, and how they are different. Lumping them together with the word 'culture' might foreclose those questions
Palaeontologists digging in the dusty wastelands of East Africa have discovered the first known chimpanzee fossil. The modest haul of just three teeth is the first hard evidence of the evolutionary path that led to today's chimpanzees. As well as shedding light on chimps, the find throws up new questions about human evolution; it seems that chimpanzees may not have been physically separated from humans as was once thought. That no one had previously found a chimpanzee fossil had long been a frustrating puzzle. Set against the many human fossils found in East Africa, the lack of specimens documenting the chimp's evolutionary story was exasperating. Part of the problem is that chimps tend to live in hot, wet jungle conditions that are not good for the preservation of remains. Humans, on the other hand, are thought to have lived for millennia on the savannah, where bones are less likely to rot. Previous theories suggested that chimps never crossed east of the Rift Valley, but instead stayed in the jungles of western and central Africa. Some even suspected that this physical separation was what set the earliest chimp and human ancestors on contrasting evolutionary voyages. But now McBrearty has stumbled on chimp remains east of this divide. This means we need a better explanation of why and how chimps and humans went their separate evolutionary ways. The discovery that chimps were living in semi-arid conditions as well as in the jungle seems to blow apart the simplistic idea that it was the shift to savannah that led to humans walking upright. The teeth are around 500,000 years old^ref. So far it is impossible to say whether they belonged to the same species as modern chimps, Pan troglodytes, or to some unnamed, now extinct ancestor. It wouldn't surprise me if there are lots of extinct chimp species. If the teeth do belong to the same species as modern chimps, this would mean the species is quite long-lived. In contrast, modern Homo sapiens has been around for only some 200,000 years. But the earlier human species H. erectus is thought to have lasted around a million years. The fossils are not old enough to tell us about the common ancestor of chimps and humans, which lived between five and seven million years ago, but this raises hope that we can find older stuff. Although there may have been more chimps living in the jungles of western Africa, there are probably more fossils in the dry eastern savannah. It's just that no one was looking for them. McBrearty hopes to return to Kenya in December to resume the search. In spite of the baking equatorial heat, December's dryness makes it the best time to probe for delicate remains.
Humans are an unusually prosocial species—we vote, give blood, recycle, give tithes and punish violators of social norms. Experimental evidence indicates that people willingly incur costs to help strangers in anonymous one-shot interactions, and that altruistic behaviour is motivated, at least in part, by empathy and concern for the welfare of others (hereafter referred to as other-regarding preferences). In contrast, cooperative behaviour in non-human primates is mainly limited to kin and reciprocating partners, and is virtually never extended to unfamiliar individuals. Experimental tests of the existence of other-regarding preferences in non-human primates show that chimpanzees do not take advantage of opportunities to deliver benefits to familiar individuals at no material cost to themselves, suggesting that chimpanzee behaviour is not motivated by other-regarding preferences. Chimpanzees are among the primates most likely to demonstrate prosocial behaviours. They participate in a variety of collective activities, including territorial patrols, coalitionary aggression, cooperative hunting, food sharing and joint mate guarding. Consolation of victims of aggression and anecdotal accounts of solicitous treatment of injured individuals suggest that chimpanzees may feel empathy. Chimpanzees sometimes reject exchanges in which they receive less valuable rewards than others, which may be one element of a 'sense of fairness', but there is no evidence that they are averse to interactions in which they benefit more than others^ref.
•  Platyrrhini; Cebidae; Cebinae; Cebus
• Cebus apella libidinosus (capuchins) in the dry caatinga forest in the northeastern Brazilian state of Piauí have an unusual approach to food: they have been caught using stones to bash the ground, then scraping away the debris to reach tasty roots and tubers, a feat previously only seen in humans. Although many primates, particularly chimpanzees and orang utans, are thought to be good at reasoning things out for themselves, digging for food has never been seen before, in the wild or in captivity. Several species are known to use 'tools', such as the birds of prey that dash their hard-shelled prey on to rocks to crack them open. But the latest case of tool use differs from many of these examples because it may be based on an understanding of cause and effect. The monkeys did not just use stones for digging. They came in handy for cracking open seeds, branches or cacti, breaking tubers into bite-sized pieces, and even pulverizing hapless lizards. The capuchins also used twigs to probe nooks and crannies for insects. Much of this behaviour is similar to that of apes such as chimpanzees and orang utans, who dig the ground with their hands. And although capuchins are known to be inventive manipulators of twigs and sticks in captivity, they don't generally manage to do anything useful with them. The fact that digging has not been seen in the species before may be down to the harsh conditions endured by the monkeys in caatinga forests, relative to the lifestyles enjoyed by other capuchins : there are times of the year when there's nothing out there apart from the odd bug and this lack of easily available food may have forced this particular band of monkeys to be more inventive. Monkeys elsewhere may not use stones simply because they never venture to the ground for fear of predators, or because the forest is too dense. Capuchins often crack open large fruits by banging them on branches, and perhaps hitting the ground with stones is simply a variant on this foraging style that happens to pay off. Capuchins' sociable nature may help such strategies to become a part of everyday life, as monkeys living side by side are likely to adopt each other's skills^{ref1, ref2}.
• Bos taurus (cow). See also transmissible and nontrasmissible diseases carried by cattle.


• Sus scrofa (pig)
• Ovis aries (sheep) : a gestation period of 147 days, provides predominantly singleton pregnancies, shows important similarities to humans in the development of the immune system. See also transmissible and nontrasmissible diseases carried by sheep.


• Canis familiaris (dog) (genome sequencing projects) : see also transmissible and nontrasmissible diseases carried by dogs.


• Felis catus (cat) : see also transmissible and nontrasmissible diseases carried by cats.


• Oryctolagus cuniculus (rabbit) : see also rabbit immune system and transmissible and nontrasmissible diseases carried by rabbits.


• Mus spp. (mouse) : most laboratory mice have contributions from ...
• Mus musculus (genome sequencing projects)
• Mus musculus castaneus (a.k.a. southeastern Asian house mouse)
• Mus musculus domesticus (a.k.a western European house mouse)
• Mus musculus molossinus
• Mus musculus musculus (eastern European house mouse)

• Mus spretus (western wild mouse)
Therefore, they should not be referred to by species name, but rather as laboratory mice or by use of a specific strain or stock name.
Ease of maintenance and breeding.
Ribs are restricted to the thoracic region, and the axial skeleton consists of 7 cervical, 13 thoracic, 6 lumbar, 4 sacral, and a variable number of caudal vertebrae. Hox genes control the patterning of the skeleton
Some biomedical research procedures using laboratory mice, such as the preparation of sex-specific fetal cell cultures, require the sex of fetuses and newborn pups to be determined. Although neonate mice can be sexed anatomically on the basis of the anogenital distance (AGD), 48% of newborn pups are reported to be unclas-sifiable using this method^ref. The existing molecular methods for sexing are PCR-based assays that combine two pairs of primers together in a multiplex reaction to amplify the Y-chromosome-specific gene Sry and an autosomal gene—either Il3 (chromosome 11) or Tshb (chromosome 3)—that serves as an internal control of PCR amplification^{ref1, ref2} : such multiplex reactions have the disadvantage, in comparison with simplex reactions, that their efficiency is heavily dependent on factors like the relative concentration of the primers, the concentration of the PCR buffer, the balance between the MgCl₂ and deoxyribonucleotide triphosphate concentrations, and the cycling conditions^ref. A novel PCR assay uses only one pair of primers in a single reaction tube to simultaneously amplify DNA fragments from both the X- and Y-chromosomes, avoiding such potential problems and permits a saving of PCR costs and preparation time. Although single cells from mouse preimplantation embryos were not included in that study, the assay also has potential utility in embryo sexing, the current method for which uses six pairs of primers in a multiplex nested PCR^ref. In conclusion, the PCR assay presented is a rapid, simple, and accurate method to distinguish fetuses and newborn pups bearing 2 X-chromosomes from those bearing one X- and one Y-chromosome^ref.
Weight : 20 g
Lifespan : mice live 3 years at most. The current oldest laboratory mouse, affectionately known as GHR-KO 11C, died just a week short of age 5 - the equivalent of a human living for 150 years - outlasting his normal peers by 2 years. Wild mice live around 25% longer than their lab-based relatives - they may possess longevity genes that have been inadvertently bred out of lab-reared animals. However the wear and tear of longer human lives contribute to a host of diseases and their small sizes (3,000 times smaller) and differences in physiology and the way drugs are metabolized limit their usefulness and mice often fail as models for humans^ref.
The limited amount of space that we provide for research animals can adversely influence the validity of behavioural data and animal welfare. Consumer demand studies have examined the strength of motivation that animals have for additional space; however, one problem of these studies is that the animals tested were generally of a gregarious species, but were tested in isolation. Some trained a single mouse from each of 6 groups to perform an operant task to gain access to an additional 319, 777, or 1600 cm² while group-housed. As the cost of visits increased, the mice continued to gain access to the additional space, although the numbers of visits and the time in the additional space decreased. The slopes of the demand functions for the three amounts of additional space ranged between 0.64 and 0.44, indicating that the mice perceived additional space to be an important resource. The slopes of the demand functions, the areas under the demand functions and the Y-axis intercepts were not significantly different between the 3 sizes of additional space, thus corroborating previous similar work. These results indicate that group-housed laboratory mice in standard laboratory cages were highly motivated for additional space, but did not discriminate between the amounts offered^ref. There is a significant effect of housing on the proportion of total fluid self-administered from the bottle containing the benzodiazepine midazolam solution (P = 0.02) vs. the non-drugged water. Mice (3 per cage) from Standard (n = 10 cages) and Unpredictable (n = 10 cages) cages drank a greater proportion than mice from Enriched (n = 6 cages) cages, indicating greater anxiety. There was also a significant effect of bottle position (P = 0.002). Mice from the Standard and Unpredictable cages drank a greater proportion of total fluid from the bottle containing midazolam solution when this was toward the rear of the cage rack, ie in a location that was less susceptible to extraneous disturbance^ref. The effects of an enriched rearing environment on 2 types of anxiety-like behavior (designated "trait" and "state" anxiety) and on spontaneous activity were investigated in 2 inbred strains of mice, BALB/c (C) and C57BL/6(B6). Subjects were socially reared from birth to 56 days of age under enriched or standard rearing conditions. The enriched environment consisted of an assembly of plastic boxes in which a various number of objects (running wheels, pieces of plastic, etc.) offered the possibility of multiple activities. The subjects were subsequently tested in 3 situations: a spontaneous activity recorder, an elevated plus-maze test (a model of state anxiety), and a free exploration test (a model of trait anxiety). No group differences could be found in spontaneous activity. Environmental enrichment, however, decreased the level of both types of anxiety-like behavior in the C strain. In contrast, the level of trait anxiety of the B6 mice was not modified. There are possible CNS modifications, especially in the limbic system^ref. Mice housed in standard cages show impaired brain development, abnormal repetitive behaviours (stereotypies) and an anxious behavioural profile, all of which can be lessened by making the cage environment more stimulating. This uninspired housing has caused concerns over animal welfare, and the validity of experiments. Stress, for example, is known to interfere with learning and memory, as well as the immune system. But regardless of this and despite the fact that there have been no data substantiating these fears, scientists have hesitated to add exciting elements to mouse cages for fear that doing so would influence the precision and reproducibility of behavioural-test results. Although the reluctance is widespread, not everyone believes in this logic. To assess the influence of animal housing conditions, they ran behavioural tests on over 400 female mice. These experiments took place in 3 different labs and compared standard cages with more exiting ones. Every few days the researchers introduced novelties such as tunnels, trapezes and tissues into the enriched cages, while the mice living in standard cages missed out. As expected, the animals in enriched cages were more confident than those from the control group. One test, known as the O-maze, illustrated this fact clearly. An O-maze is a circular track elevated above the ground with protective areas on either side. Generally, mice prefer to stay in the sheltered parts for fear of being exposed to the open, brightly lit parts of the track. The study demonstrated that mice who lived in stimulating environments spent about twice as much time in these exposed areas as compared with their control counterparts. From now on people can't hide behind a scientific argument. But although researchers noticed a difference between mice from enriched and barren cages, crucially they found that results from the enriched group remained as stable across the 3 labs as those from the control group. In other words, increasing the animals' quality of life did not make the results from different labs any more variable. Environmental enrichment increases neither individual variability in behavioural tests nor the risk of obtaining conflicting data in replicate studies. The housing conditions of laboratory mice can be markedly improved without affecting the standardization of results. The study is the first to assess such effects using simultaneous tests in multiple labs^ref. No one knows exactly why the mice housed in interesting cages are less stressed, but probably animals feel more in control of their environment when they can respond to new threats. Mice living in enriched conditions, for example, have the option of hiding behind objects placed in their cages when scared by humans. Standardization of cages reduces the number of live mice needed for experiments : for numbers to be kept to a minimum it is important that sources of variation are controlled, but housing designed for the animals' physical and behavioural requirements need not compromise this objective. Animals kept in laboratory conditions are significantly stressed. Others believe that what is needed is more research into non-animal alternatives and there is no avoiding that animals kept in laboratory conditions are significantly stressed, and no amount of enrichment studies will prevent this. Before intramuscular injections mice are anesthetized with ketamine-xylazine (70 and 10 mg/kg of body weight, respectively). Drugs should be injected into the tibialis anterior  in a volume of 25 mL after a small incision is made to expose the muscle. The incision is closed with Vicryl suture.
The most commonly used strains are :
• cancer-free white (C.F.W.) mouse : one of a strain of mice bred for use in cancer research laboratories.
• New Zealand black (NZB) mouse : a mouse of an inbred strain that develops an autoimmune disease closely resembling human systemic lupus erythematosus
• C57BL mice^ref: Black, a.

Origin: Little 1921 from the mating of female 57 with male 52 from Miss Abbie Lathrop's stock. The same cross gave rise to strains C57L and C57BR. Female 58 mated with the same male gave rise to strain C58. C57BL is probably the most widely used of all inbred strains (substrain C57BL/6 alone accounts for over 14% of occasions on which an inbred strain is used), though in many ways it seems to be atypical of inbred strains of laboratory mice. In contrast to 36 other standard inbred strains, it carries a Y chromosome of Asian Mus musculus origin (c.f. AKR and SWR)^ref, and a LINE-1 element derived from Mus spretus the frequency of which suggests that up to 6.5% of the genome may be of M. spretus origin^ref. A probe designated B6-38 to the pseudoautosomal region of the X and Y chromosome has a characteristic PstI pattern of fragment sizes which is present only in the C57BL family of strains^ref. It usually has a good breeding performance, depending on substrain, and has been used as the genetic background for a large number of congenic strains covering both polymorphic and mutant loci. 4 major substrains A, GrFa, 6 and 10 appear to be quite similar, and any differences are consistent with what might be expected from the accumulation of new mutations and a small ammount of residual heterozygosity, though it has been found that B6 and B10 differ at multiple loci on chrosome 4 including the microsatellite markers D4Mit69, D4Mit71 and D4Mit72^ref. Additional microsatellites which distinguish between B6, B10 and C57BLKS are given^ref. The former Ks substrain differs at several loci probably as a result of genetic contamination with a DBA substrain. This has been re-named C57BLKS, and is listed separately. The 7 major substrains existing in 1935 are listed below.
Behaviour (substrain unspecified) : high incidence of tail rattling (1/5) (St. John, 1973). Short latency to attack and eat crickets (2/7)^ref. High alcohol (ethanol) preference ratio (1/5) (McClearn, 1965). Short latency to emerge from home cage (1/7), short latency to cross barrier in open-field (1/7), low number of stairs climbed (7/7), low urination (6/7) and defaecation (7/7) (McClearn et al., 1970., 1970).
Life-span and spontaneous disease (substrain unspecified) : mammary tumours < 1%^ref. Lung adenomas 0-9% in LiA substrain (Mühlbock and Tengbergen, 1971). Zero incidence of mammary tumours at 2 years (cf. 3/7)^ref. Mean life-span 800 days in males and 750 days in females^ref, who also give details of pathology in a large aging colony of C57BL/Icrf-at mice. Hyperphalangy and polydactyly occur with a low incidence in all C57BL strains and substrains (Dagg, 1966). Hydrocephalus 4.1%^ref. Type B reticulum cell neoplasms 75% at about 20 weeks in HeDe substrain^ref.
Anatomy (substrain unspecified) : low proportion of basophilic cells in adenohypophysis (5/5)^ref
Drugs (substrain unspecified) : resistant to induction of adenocarcinomas of the colon by 1, 2-dimethylhydrazine (cf. 2/4)^ref. Resistant to induction of pulmonary tumours (6/6) and leukaemia (5/6) by neonatal administration of DMBA^ref. Susceptible to the induction of pulmonary fibrosis by bleomycin (contrast C3Hf/Kam)^ref and irradiation, though the sensitivity of lung fibroblasts to irradiation in-vitro does not correlate with in-vivo sensitivity^ref (Dileto and Travis, 1996). Sensitive to the development of uterine tumours following treatment with DMBA at 4-weeks of age (cf 3/6)^ref (Tsubura et al, 1993). Resistant to induction of mammary tumours by urethane (7/7)^ref. Pituitary adenoma induced in most mice by oestrogens (Heston, 1963). Resistant to skin tumour induction by methylcholanthrene (5/5)^ref. Susceptible to fibrosarcoma induction by methylcholanthrene (4/15 males, 3/15 females)^ref. Resistant to chloroform toxicity (cf. 5/9)^ref. Resistant to induction of cleft palate by cortisone (4/5) (Kalter, 1965). Resistant to lethal effects of ozone (22/22)^ref. Resistant to colon carcinogenesis by 1,2-dimethylhydrazine (cf. 4/7)^ref.
Immunology (substrain unspecified) : poor immune response to low levels of bovine g-globulin (cf. 4/8)^ref. Poor primary immune response to bovine serum albumin (6/6)^ref. Poor primary immune response to sheep erythrocytes (3/6 to 6/6, depending on test and dose)^ref. Poor immune response to Vi antigen (cf. 3/5)^ref (Gaines et al., 1965., 1965). Low antibody affinity (7/7) and small quantity of antibody production (6/7)^ref. Low antibody affinity to HSA (9/9)^ref.
Infection (substrain unspecified) : resistant to oncogenic effects of polyoma virus given at birth^ref. Resistant to Mycobacterium marinum (2/9) and poor plateau harvest of M. leprae 8 months after infection (9/9)^ref
• C57BL/6 mice : Inbr (J) 150.

Origin: As a boy, Clarence Cook Little kept mice as pets, but his hobby became serious inquiry when he began studying Mendelian inheritance of mouse coat color under William Castle at Harvard University. Wilhelm Johannsen, the Danish botanist who coined the term "gene," showed the value of inbreeding to fix characteristics, and Little applied that idea to mice. In 1909, he produced the first inbred mouse strain, DBA, from repeatedly mating brother-sister pairs. Against a "fixed" genetic background, Little sought to sort a trait far more complex than coat color: cancer susceptibility. DBA, however, showed certain frailties from inbreeding that compromised its usefulness when more resilient strains came along. Sometime around 1914, Little obtained a female mouse, code numbered 57, and a male, numbered 52, which he inbred through at least 20 generations (3-4 generations a year). He named the resulting strain C57BL/6 (a J was added later to indicate the Jackson Laboratory, which Little founded in 1929)^ref. The upper-case C may have distinguished this black-coated mouse from the lower-case c for a recessive albino strain. The number 6 referred to one of multiple lines within the strain, among others that did not survive inbreeding pressure. Though C57BL/6J or "black six" had some inherited weaknesses, it was a good breeder, and showed delayed senescence of its hematopoietic system compared to DBA. Eventually, it became the most widely used strain of inbred mouse for the study of mammalian genetics, and it was the first nonhuman mammal to be sequenced in 2002^ref
Substrains 6 and 10 were separated prior to 1937. This substrain is now probably the most widely used of all inbred strains. Substrain 6 and 10 differ at the H9, Igh2 and Lv loci. Maint. by J,N, Ola.
Behaviour : high alcohol (ethanol) preference (1/4) (Fuller, 1964b), (2/18) (Rodgers, 1966). Achieve blood alcohol levels of 60 mg% when access to alcohol is restricted to 60 mins. per day^ref. Alcohol preference may be associated with strain differences in mesolimbic enkephalin gene expression (Ng et al, 1996). A quasi-congenic QTL introgression strain carrying a low alcohol consumption gene from BALB/c has lower voluntary alcohol consumption than C57BL/6, with 96% of loci in common^ref. Low severity of ethanol withdrawal symptoms compared with DBA/2, possibly associated with differences in neuroactive steroid sensitivity^ref. Alcohol preference is due to at least two recessive quantitative trait loci that are sex-restricted in expression^ref. Low `emotionality' (12/15), high open-field exploration (2/15)<sup>ref</sup>. High spontaneous locomotor activity (8/9)<sup>ref</sup>. Short time of immobility in a forced swimming test (8/9)<sup>ref</sup>. Low shock-avoidance learning (7/9)<sup>ref</sup>. Low shuttle-box avoidance (5/5), high wheel activity (1/5)<sup>ref</sup>. Rapid shock-avoidance learning (2/7) and slow extinction (6/7)<sup>ref</sup>. High shock-avoidance learning (1/8)<sup>ref</sup>. High radial-arm maze learning (1/3)<sup>ref</sup>. High locomotor activity (1/5)<sup>ref</sup>. High locomotor activity when grouped (2/6) and single (1/6)<sup>ref</sup>. Resistant to audiogenic seizures (11/11)<sup>ref</sup>. Relatively insensitive to the primary odorant isovaleric acid (contrast 7 other strains) and may provide an animal model of specific anosmia<sup>ref</sup>. Low balsa-wood gnawing activity (2/16) Fawdington and Festing (1980). High preference for sweet tasting substances (saccharin, sucrose, dulcin and acesulfame, averaged) (1/26)<sup>ref</sup> . Rejects saline at moderate concentrations (contrast 129)<sup>ref1, ref2</sup>. Feed restriction for 9 days failed to cause stereotypic cage cover climbing (contrast DBA/2)<sup>ref</sup>
Life-span and spontaneous disease : primary lung tumours 1% in males, 3% in breeding females and zero in virgin females. Lymphatic leukaemia less than 2%, mammary adenocarcinomas less than 1%<sup>ref</sup>. Leukaemia 7%<sup>ref</sup>. Rare "lipomatous" hamartomas or choristomas have been noted<sup>ref</sup>. Susceptible to the development of atheromatous lesions on wall of aorta after 20 weeks on a high-fat diet. Develop fatty streak-like lesions in the valve sinus region of the ascending aorta after 10-20 weeks on a diet enriched in saturated fat and cholesterol. After a further 15 weeks fibro-fatty lesions with many of the characteristics of human atheromatous plaques are found<sup>ref</sup>. Exhibit aortic cartilaginous metaplasia (contrast C3H)<sup>ref</sup>. Susceptible to diet-induced aortic fatty streak lesions which correlates with a low level of paroxinase mRNA (contrast C3H)<sup>ref</sup>. Develops non-insulin-dependent diabetes mellitus and hypertension when fed a high fat-high simple carbohydrate diet, whereas A/J mice do not<sup>ref</sup>. Susceptible to the development of atherosclerosis on a semi-synthetic high fat diet (1/9)<sup>ref</sup>. Blood glucose levels and insulin insensitivity in crosses between diet-induced type II diabetes sensitive C57BL/6 and resistant A/J are genetically independent<sup>ref</sup>. High simple carbohydrate diet for five months induced hyperglycemia, hyperinsulinemia and hypercholesterolemia and non-insulin-dependent diabetes mellitus which appeared to be associated with the metabolic characteristics of visceral fat<sup>ref</sup>. Gain more weight on high fat diets without consuming more calories than A/J mice and develop adipocyte hyperplasia. However, animals fed a low fat, high sucrose diet were leaner than those fed a high-complex-carbohydrate diet. These results suggest that genetic differences in metabolic response to fat is more important in the development of obesity and diabetes than caloric intake<sup>ref</sup> (Surwit et al, 1995). Loci on chromosomes 1, 3, 5 and 11 are associated with variation in high density lipoprotein levels with coordinate expression of cholesterol-7-a hydroxylase in a cross involving atherosclerosis resistant C3H/HeJ mice<sup>ref</sup>. Hepatic stearoyl CoA desaturase mRNA levels significantly elevated compared with atherosclerosis-resistant BALB/c mice, and was reduced in mice fed a high fat diet<sup>ref</sup>. Congenital abnormalities 10%, including eye defects, polydactyly and otocephaly (Kalter, 1968). Microphthalmia and anophthalmia 8-20% and hydrocephalus 1-3% (Dagg, 1966). Occular defects appear to be due to defects in development of the lens<sup>ref</sup>. Develop spontaneous auditory degeneration with onset during young adulthood, with enhanced susceptibility to acoustic injury and delayed effects of toluene (contrast CBA/Ca)<sup>ref1, ref2</sup>. This is associated with early hair cell changes including bent and fused stereocillia, bulging of the cuticle plates, hair cell loss and swelling of affected dendrites<sup>ref</sup>. Carry a single recessive gene different from that found in BALB/cBy and WB/ReJ, causing age-related hearing loss<sup>ref</sup>. Hearing loss is caused by degeneration of the organ of Corti, originating in the basal, high frequency region and then proceeding apically over time. This results in a severe sensorineural hearing loss by 14 months of age<sup>ref</sup>. More susceptible to noise-induced hearing loss than CBA/J<sup>ref</sup>. Life-span above average in both sexes in conventional conditions (17/22 = 676 days in males, 18/22 = 692 days in females)<sup>ref</sup>. Life-span 827 _ 34 days in males, 818 _ 21 days in females<sup>ref</sup>. Life-span 878 _ 10 days in males and 794 _ 6 days in females<sup>ref</sup>. Median life-span 600 days<sup>ref</sup>. Gross tumour incidence 70%, maximum life-span about 1200 days in SPF conditions (Mewissen, 1971). Dermatitis with intense pruritis leading to self-mutilation and death, and sometimes associated with the mite Myobia musculi appears to be more severe in this strain than others<sup>ref</sup>. Impaired axonal regeneration involving multiple genetic loci<sup>ref</sup>.
Normal physiology and biochemistry : low plasma cholesterol at 12 and 24 weeks (8/8)<sup>ref</sup>. Low plasma triglyceride levels (1/11 in By and 3/11 in J substrains) and low plasma cholesterol (2/11 in By and 4/11 in J substrains)<sup>ref</sup>. Low serum ceruloplasmin levels in males (24/26) but intermediate in females (Meier and MacPike, 1968). High blood sugar (3/12)<sup>ref</sup>. Low serum cholesterol (5/5) in C57BL/6-ata<sup>ref</sup>. Arterial blood has a low pH (10/10) (Bernstein, 1966). Low concentration of prostaglandin F in epididymis (6/6)<sup>ref</sup>. High liver tyrosine aminotransferase in fasted mice (3/10) but low in C57BL/6-ob (10/10) (Blake, 1970). Low brain L-glutamic acid decarboxylase (GAD) (7/7) and acetylcholinesterase activity (7/7) but high catechol-O-methyltransferase activity (2/7)<sup>ref</sup>. Low calcium uptake by the heart (4/5)<sup>ref</sup>. Low sensitivity to thyrotropin (20/21)<sup>ref</sup>. High brain sulphatide (1/5)<sup>ref</sup>. High hepatic benz (a) pyrene hydroxylase activity (1/6)<sup>ref</sup>. Low hepatic d-aminolaevulinate dehydratase activity (8/8)<sup>ref</sup>. High aldehyde dehydrogenase and alcohol dehydrogenase activity compared with DBA/2<sup>ref</sup>. High metabolism of 131I with low 48 h retention (1/6)<sup>ref</sup>. High liver arylsulphatase activity (1/12)<sup>ref</sup>. Low porphyrin content of Harderian gland (16/16)<sup>ref</sup>. Low hepatic urokinase activity (4/6 to 6/6) but high hepatic histidine ammonia-lyase activity (1/6 to 2/6 in two substrains)<sup>ref</sup>. Low basal levels of kidney catalase (4/4), superoxide dismutase (4/4) and renal glutathione reductase (4/4)<sup>ref</sup>. Iron overload causes inhibition of hepatic uroporphyrinogen decarboxylase and uroporphyria in C57BL/10ScSn but not DBA/2 mice. This was not correlated with the Ah locus in a study involving 12 mouse strains<sup>ref</sup>. Low levels of apoA-IV messenger RNA in liver compared with 129/J<sup>ref</sup>. Low susceptibility to audiogenic seizures (6/6)<sup>ref</sup>. Long tau DD, the endogenous (free-running) period of the circadian pacemaker measured in constant environmental darkness (12/12)<sup>ref</sup>. Has defective secretory group II phospholipase A2 gene (cf strains 129/Sv and B10.RIII)<sup>ref</sup>. Susceptible to severe hypercapnia with hypoxia assessed by elevated minute ventilation rate (1/8)<sup>ref</sup>. Has a rapid and shallow breathing pattern phenotype (contrast C3H)<sup>ref</sup>. Susceptible (1/7) to cerebral ischemia following bilateral carotid occlusion with 90% of mice showing typical neuological signs such as torsion of the neck and rolling fits with selective neuronal death in the hippocampus and caudoputamen after 20 minutes of ischemia<sup>ref</sup>
Anatomy : small kidney/body weight ratio (19/21)<sup>ref</sup>. Large thyroid (1/5)<sup>ref</sup>. High total leukocyte count (2/18), low erythrocyte count (14/18)<sup>ref</sup>. Small hippocampus (9/9)<sup>ref</sup>. Accessory spleens in about 32% of mice (2/9) and low number of Peyer's patches (7/7) (Hummel et al., 1966). Higher bone mass than A/J<sup>ref</sup>. Low number of haematopoetic stem cells in bone marrow (contrast DBA/2)<sup>ref</sup>. Less susceptible to the development of micronuclei than BALB/c following treatment with clastogenic base analogues and nucleosides<sup>ref</sup>. High level of spontaneous sister chromatid exchange (4/4)<sup>ref</sup>. A detailed staging of these mice between gestation days 11 and 13 (Theiler's stages 18 and 21) has been published<sup>ref</sup> by Miyake et al, (1996). Hematopoetic stem-cell pool 11-fold lower than in DBA/2. This is largely due to loci on chromosome 1<sup>ref</sup>. Low bone density of femur (11/11)<sup>ref</sup>. The timing of onset and duration of condensation and onset of matrix formation of first arch cartilages has been described<sup>ref</sup>. A detailed staging table to facilitate study of cranial skeletal development every 2hrs. between days 11 and 13 of gestation has also been described<sup>ref</sup>
Drugs : susceptible to skin ulceration by DMBA (cf. 13/22) (Thomas et al., 1973., 1973). Susceptible to induction of subcutaneous tumours by 3-methylcholanthrene (3/14)<sup>ref</sup>, (1/12)<sup>ref</sup>. High incidence of lymphomas after methylcholanthrene administration by gavage (2/5)<sup>ref</sup>. Susceptible to toxic effects of DMBA (6/6) (Schmid et al., 1966., 1966). Pre-treatment with beta-naphthoflavone 48 hr. before administration of N-nitrosoethylurea (ENU), once weekly for 4 weeks caused a significant doubling in the number of lung tumor bearers (contrast 4 strains)<sup>ref</sup>. Phenobarbitone in the diet to give an intake of 85mg/kg per day resulted in 4% of animals developing basophilic nodules by 91 weeks of age (contrast 70% in C3H/He), but no increase in liver carcinomas<sup>ref</sup>. However, there was a 2-fold lower level of DNA synthesis in C57BL/6 mice relative to C3H mice after partial hepatactomy, though partial hepatectomy is a tumour promoter in C57BL/6 but not in C3H mice<sup>ref</sup>. Sensitive to teratogenic effects of acetazolamide (2/6)<sup>ref</sup>. Resistant to teratogenic effect (cleft palate) by cortisone acetate (2/6)<sup>ref</sup> (Kalter 1981). Hepatic epoxide hydrase activity induced by pentobarbital i.p. (cf. 4/7) (Oesch et al., 1973., 1973). Resistant to teratogenic effects of cortisone acetate (4/4)<sup>ref</sup>. Resistant to lethal effects of ozone (16/21)<sup>ref</sup>, but susceptible (cf 5/8) to ozone-induced decreases of tracheal potential<sup>ref</sup> and to airway inflammation (contrast C3H/He)<sup>ref</sup>. Susceptible to ozone-induced lung inflammation, which is exacerbated by vitamin A deficiency<sup>ref</sup>. High incidence of convulsions induced by flurothyl (1/5)<sup>ref</sup>. Susceptible to hyperbaric oxygen (4/18)<sup>ref</sup>. Resistant to chloroform toxicity (cf. 5/9)<sup>ref</sup>. Resistant to toxic effects of isoniazid (2/10)<sup>ref</sup>. Sensitive, as judged by eosinophil response, to cortisone acetate (cf. 3/6)<sup>ref</sup>. High (89%) ovulatory response to 3 I.U. of PMS in immature mice (2/6), but only a 56% response to 7 I.U. No facilitation by exposure to males at these doses<sup>ref</sup>. High locomotor activity after treatment with D-amphetamine (1/6)<sup>ref</sup>. Nicotine increases learning ability (1/9)<sup>ref</sup>. Resistant to colon carcinogenesis by 1,2-dimethylhydrazine (cf. 4/7)<sup>ref</sup>. Low ED<sub>50</sub> to behavioural effects of nicotine (3/19)<sup>ref</sup>. High self-selection of nicotine (1/6) which is inversely correlated with sensitivity to nicotine-induced seizures<sup>ref</sup>. Low bronchial reactivity (6/6) to methacholine and serotonin<sup>ref</sup>. Resistant (6/8) to daunomycin-induced nephrosis<sup>ref</sup>. Low (10/10) neural sensitivity to pentylenetetrazol convulsions<sup>ref</sup>. Susceptible to biliary tract injury following oral dosing with 500 micrograms of the fungal toxin sporidesmin (1/4)<sup>ref</sup>. Low histamine release from peritoneal mast cells induced by compound 48/80, a calcium dependent histamine releaser ( c.f. 5/8)<sup>ref</sup>. Low histamine release from peritoneal mast cells induced by Ca<sup>2+</sup> ionophore A23187 ( c.f. 1/8, contrast BALB/c, C3H/He, DBA/2 etc.)<sup>ref</sup>. Carries gene (Tpmt) for low levels of thiopurine methyltransferase activity, catalyzing the S-methylation of 6-mercaptopurine and other heterocyclic and aromaticthiol compounds (like AKR, unlike DBA/2)<sup>ref</sup>. More sensitive to acute toxic effects of aflatoxin B-1 than strains CBA/J or BALB/c<sup>ref</sup>. Airways hyporeactive to acetylcholine (c.f. 3/7)<sup>ref</sup>. High voluntary comsumption of morphine in 2-bottle choice situation<sup>ref</sup> (1/15). Estrogen induces an increase in VLDL and LDL-cholesterol (like C57L, contrast BALB/c and C3H)<sup>ref</sup>. 9-fold higher ED<sub>50</sub> for haloperidol-induced catalepsy than DBA/2, but this is not associated with numbers of cholinergic neurons<sup>ref</sup>. Accumulates three to 5-fold lower levels of mercury in liver and blood than DBA/2 or A.SW after 4 weeks exposure to mercuric chloride, but higher levels in spleen following 8-12 weeks of exposure<sup>ref</sup>.
Immunology : genetic bias to T<sub>h</sub>1 responses<sup>ref1, ref2</sup>; high susceptibility to induction of amyloid by casein (1/6)<sup>ref</sup>. Poor immune response to type III pneumococcal polysaccharide (4/5)<sup>ref</sup>. Poor immune response to synthetic dsRNA (6/7)<sup>ref</sup>. Good immune response to cholera A and B antigens (2/8)<sup>ref</sup>. Resistant to induction of anaphylactic shock by ovalbumin (cf. 6/13) (Tanioka and Esaki, 1971). Rapid rejection of about 76% of male skin isografts by females by 25 days (1/10)<sup>ref</sup>. Poor immune response to GAT (random terpolymer of Glu60, Ala30, Tyr10) (9/10)<sup>ref</sup>. Good immune response to Salmonella senftenberg (1/5) and S. anatum (2/5) lipopolysaccharide<sup>ref</sup>. Non-responder to synthetic polypeptide Glu57, Lys38, Ala5 (cf. 4/7)<sup>ref</sup>. High sporadic occurrence of natural haemagglutinins to sheep red blood cells<sup>ref</sup>. Discriminator between `H' and `L' sheep erythrocytes (cf. 12/18)^ref. Poor immune response to Pro-Gly-Pro-ovalbumin (7/7) and (Pro66, Gly34)_n (6/7) but good immune response to (Pro-Gly-Pro)_n (1/17)^ref. High (2/6) PHA- stimulated lymphocyte blastogenic response^ref. Erythrocytes have low agglutinability (cf. 11/25)^ref. High immune response to ferritin in B6-Tla (2/16)^ref. Low responder to dextran (cf. 6/10)^ref. Low responder to E. coli ß-D-galactosidase, with "memory" developing in absence of antibody formation^ref. Precipitating and skin sensitising antibodies have slow electrophoretic mobility (6/6)^ref. Resistant to anaphylactic shock^ref. Susceptible (1/5) to induction of autoimmune prostatisis (contrast BALB/c)^ref. High expression of neutral glycosphingolipid GgOse(4)Cer in concanavalin A stimulated T lymphoblasts (cf 3/6)^ref. Anti-BPO IgE monoclonal antibody produced potent systemic sensitization sufficient for provocation of lethal shock in most aged (6 to 10 months) mice (c.f. 3/8)^ref. Susceptible to immunosuppression of contact hypersensitivity by UVB light (cf 3/18)^ref.
Infection : Develops a slowly progressing parasitosis ("low responder") after infection with the Cornell strain of Toxoplasma gondii^ref. Did not support sustained growth of 6 strains of Leishmania mexicana mexicana (contrast BALB/c)^ref. Resistant to Leishmania major (contrast BALB/c)^{ref1, ref2}. Susceptible to L. major mexicana, and vaccination against the parasite using liposomes with parasite membrane antigens was effective (cf CBA/Ca but contrast C57BL/10) (Lazama-Davila, 1997). Susceptible to Salmonella typhimurium strain C5 (1/5) (Robson and Vas, 1972). 100-fold more resistant to Listeria monocytogenes than A/J when measured by median lethal dose^ref. This seems to be associated with increased levels of IFN-g and GM-CSF compared with susceptible A/J mice^ref. Resistant to Mycoplasma fermentans (6/6)^ref. Resistant to Mycoplasma pulmonis infection (cf 4/16)^ref. Resistant to infection by Mycobacterium marinum (6/6)^ref. Resistant to infection by liver fluke Opisthorchis felineus (6/6) (Zelentsov, 1974). Resistant (1/4) to infection with the helminth worm Angiostrongylus costaricensis^ref (Ishii and Sano 1989). Relatively susceptible to infection with Helicobacter felis (contrast C57BL/6)^ref. Susceptibile to infection by Helicobacter felis with moderate to severe chronic active gastritis in the body of the stomach, which increased over time (cf 4/6)^ref. H. felis induces hypertropic gastropathy^ref. Highly resistant to MMTV which is thought not to be carried by the strain^ref. Resistant to HSV (2/11)^ref. Resistant to HSV-1 (contrast BALB/c)^ref. Susceptible to mouse hepatitis virus type 3 infection (cf. 5/14)^ref. Develops antibodies to mouse hepatitis virus which can be reliably detected by the complement fixation test, in contrast to 5 other strains^ref. Low mortality in a natural epizootic of ectromelia (7/8)^ref. High expression of RNA tumour virus group-specific antigen in some substrains (1/8) but low in others (7/8)^ref. Resistant to development of leukaemia on infection by Friend virus (cf. 2/11)^ref. Resistant to diabetogenic effects of ECMV, but treatment with carrageenan to compromise macrophage function makes the mice susceptible^ref. Susceptible to measles virus induced encephalitis, which correlates with a high CTL response (like C3H, contrast BALB/c)^ref. Resistant to the development of tumours following inoculation with polyoma virus (Freund et al, 1992). Resistant (6/7) to the development of chronic Chagas' cardiomyopathy in postacute Trypanosoma cruzi infection^ref. Resistant to infection with Trypanosoma congolense with an initial peak of parasitemia on day 6, followed by rapid apparent clearance in an average of 3 days (contrast BALB/c)^ref. Infection with larval Echinococcus multilocularis by transportal injection of hydatid homogenate results in a multivesiculation form of hydatid development (cf 4/9)^ref (Nakaya et al, 1997). Resistant to tumorigenesis induced by polymoa virus (1/9), in contrast with C3H/Bi (Freund et al 1992). Susceptible to mouse adenovirus type 1 which causes a fatal hemorrhagic encephalomyelitis (contrast BALB/c)^ref. Less susceptible to Streptococcus suis type 2 including the type strain, 2 isolates from meningitis in pigs and two isolates from tonsils of clinically healthy pigs (c.f. 3/5)^ref. Resistant to carditis on infection with Lyme borreliosis (Borrelia burgdorferi) (contrast C3H, SWR, BALB/c)^ref. Thymectomized C57BL/6 mice that were intravenously infused with monoclonal antibody to selectively deplete CD4⁺ T cells are susceptible to disseminated Mycobacterium avium infection. The increased susceptibility is comparable to that of C57BL/6-bg. The course of such infections can be markedly restrained and in some cases the infections can be sterilized by treatment over a 120-day period with the antimycobacterial agent rifabutin^ref. Susceptible to infection with M. avium strains 101 and 2-151, and can be used to test anti-mycobacterial agents^ref. Susceptible to infection with M. paratuberculosis (contrast C3H/HeJ)^ref. Resistant to infection with Yersinia enterocolitica associate with a good IFN-g response (contrast BALB/c)^ref. Susceptible, with high amylase response to the fungus Paracoccidioides brasiliensis (cf 6/12)^ref. Mouse mammary tumor proviral loci have been identified^ref. Resistant (1/10) to infection with Ehrlichia risticii^ref. Highly susceptible to Plasmodium berghei with all mice developing erythrocytic infection following intravenous injection of 50 sporozoites. The same level of infection could only be established in BALB/c with 10,000 sporozoites^ref. Infection with P. berghei results in low blood parasitemia and death with neuological symptoms within 8-10 days, in contrast with the more resistant BALB/c^ref. Resistant to chronic weakness and inflammation following infection with Tucon strain of coxsackie virus B1, in contrast with C57BL/10 and B10 congenic strains^ref
Reproduction : good reproductive performance (3/8). Litter size 6.2 _ 0.2, sterility 8%^ref. Large litter size (1/6), mean 6.2^ref. Good breeding performance, 2.5 young/female/month (2/24) (Hansen et al., 1973., 1973). Has longer and more regular oestrus cycles than DBA/2 and C3H/HeJ^ref (Nelson et al 1992). Late opening of vagina and first cornification (3/3), but early onset of cyclicity compared with C3H^ref. Mice carrying the Y-chromosome from Mus musculus domesticus from Tirano (Italy) or M.m. poschiavinus from Poschiavo (Switzerland) fail to develop normal testes but instead develop ovaries and ovotestes. Some hermaphroditic males become fertile, but the XY females lack normal gonadal steroids and can not carry pregnancy to term. There is delayed expression of IGF-I which may be responsible for the low setroid expression^ref (Villapandofierro et al, 1996).
Miscellaneous : high degree of genetic distinctiveness (4/27)^ref. Recommended host for the following transplantable tumours: mammary adenocarcinoma BW 10232 melanoma B16, myeloid leukaemia C 1498 and preputial gland carcinoma ESR586^ref. Embryonic stem cell lines have been established^ref. High rate of spontaneous mutations at the agouti and W loci (1/21)^ref
• BALB/c^ref : Albino: A,b,c.

Origin : Stock acquired by H.Bagg in 1913, to MacDowell, to Snell in 1932 (who added the /c). Now widely distributed and among the top 2-3 most widely used inbred strains. The strain is particularly well known for the production of plasmacytomas on injection with mineral oil. These tumours form the basis for the production of monoclonal antibodies. Used as a general-purpose strain in many different disciplines. Good breeding performance and long reproductive life-span. Normally has low mammary tumour incidence but can be infected with the mammary tumour virus by fostering to C3H (which carries the virus), and it then gets a high incidence of mammary tumours. The history and characteristics of the strain have been reviewed by Potter (1985). 3 major substrains trace back to before 1940 :
• BALB/cHeAn : Inbr ?.To Snell circa 1932, to He circa 1935. Now widely distributed (including the By, AnN, HeA and AnPt substrains). This substrain is much less aggressive than the J substrain. Maint. by A, N.
• BALB/cJ : Inbr 150 +?.Snell to Jackson Laboratory after 1940. Males of this substrain are extremely aggressive and will fight if housed together once mature. The Lac substrain separated in 1952 is non-aggressive. Maintained by J, Ola (JLac substrain).
• BALB/cRl : Inbr ?. Snell to Green circa 1937, to W.L. and L.B.Russell c1948
Data on genetic markers suggest that these substrains have diverged largely through mutation or residual heterozygosity rather than genetic contamination. The substrains differ as a result of mutations at the Raf1 locus (controlling the expression of alpha-fetoprotein), the Qa2 locus (governing cell surface antigens), the Gdc1 locus (governing L-glycerol 3-phosphate dehydrogenas activity in the liver) and the PR1 repetative sequence^ref. There is no evidence for genetic contamination during the early history of the strain. A fourth substrain, BALB/cWt is also listed as it has a 3% incidence of true hermaphroditism, which significantly distorts the sex ratio^ref
Behaviour : high intrastrain aggression (4/14), low open-field activity (12/14), high tail rattling but low social grooming (14/14) during aggressive encounters (Southwick and Clark, 1966,1968). Low open-field activity (13/15)^ref. High spontaneous locomotor activity (7/9)^ref. Long time of immobility in a forced swimming test (1/9)^ref. Short latency to cross barrier in maze (2/7), high urination (2/7) and defaecation (1/7) in test apparatus (McClearn et al., 1970., 1970). Low wheel activity^ref. Low avoidance conditionability (9/9)^ref and low shock avoidance learning in males (6/6)^ref. Poor shock avoidance learning (7/8)^ref. Low alcohol preference ratio (4/5) (McClearn, 1965), (13/18) (Rodgers, 1966). High social dominance of males in competition for females (2/6) (DeFries and McClearn, 1970). High balsa-wood gnawing activity (14/16) (Fawdington and Festing 1980). Exhibit hypersecretion of corticosterone and marked brain catecholamine alterations and disruption of Morris water maze performance following stressors such as foot-shock. However, performance deficits were prevented by cross fostering to C57BL/6 foster mothers^ref.
Life-span and spontaneous disease : life-span intermediate in both sexes in conventional conditions (12/22 = 539 days in males, 11/22 = 575 days in females)^ref. Life-span intermediate in males (7/17 = 509 days) and short in females (4/17 = 561 days) in SPF fostered conditions^ref. Life-span 648 _ 20.6 days in females and 816 32.4 days in males^ref. Life-span 20 months in females and 13 months in males. Amyloidosis 40% in males. Reticular neoplasms 23% females and 3% males^ref. Primary lung tumours 32% in males, 30% in breeding females and 14% in virgin females in Scott substrain. Leukaemia 5%^ref. Zero incidence of lymphatic leukaemia. Mammary adenocarcinomas zero in males, 5% in breeding females and 1% in virgin females^ref. Mammary tumours 30% at 2 years (3/7)^ref. Mammary tumours 20% in females at 16.7 months, but 100% at 7.1 months in BALB/cfC3H^ref. Mammary tumours 10% at 14 months^ref. Low gross tumour incidence in males (20/22) (Storer, 1966). Renal tumours 25-48%, mammary tumours 3-13%, reticuloendothelial tumours 11-20%, lung tumours 10-16%, synoviomas 2-8%, depending on substrain^ref. Low incidence of virus-like particles in chemically induced sarcomas^ref. Frequency of rhabdomyosarcomas was calculated to be 2.4/100,000 mice retained as breeders, and 10/14 mice found with these tumours were of the BALB/cJ substrain. Rare spontaneous myoepitheliomas arising from myoepithelial cells of various exocrine glands have been observed in the J and ByJ substrains^ref. Gross tumour incidence in germ-free mice 43%, with lung tumours 21%, angiomas 6%, lymphosarcomas 5% and other tumour types less than 3% each (Smith and Pilgrim, 1971). Pulmonary tumours 26-29% (Heston, 1968). Left auricular thrombosis occurs in 66% of older breeding females. This is associated with reduced levels of the prothrombin complex factors such as factor IX (40% of normal), factor XIII (60% of normal), factor X (50% of normal) and prothrombin (about 33% of normal). These deficiencies occur slightly before parturition (Meier and Hoag, 1966). High incidence of epicardial mineralisation (11% in males, 4% in females), which increases slightly with age^ref. Heart defects, including cardiac calcinosis 17-62%^ref. Spontaneous myocardial lesions of right ventricle found in 60% of females and 30% of males. These macroscopically visible degenerative fibrosclerotic lesions may represent a last phase of myocarditis of the inflammatory type found in apparently normal mice^ref. Carry a single recessive gene different from that found in C57BL/6J and WB/ReJ, causing age-related hearing loss^ref. Zero incidence of spontaneous congenital malformations (cf. 2/9) in GrKt-tk substrain (Kalter, 1968).
Normal physiology and biochemistry : high Na/K ratio in erythrocytes (2/9)^ref. Low levels of serum ceruloplasmin in males (26/26)^ref (Meier and MacPike, 1968). Low serum haptoglobin level (9/11)^ref. High systolic blood pressure (2/19)^ref. Low mean heart rate (6/7) but high heart rate adaptation (3/7)^ref. Low plasma cholinesterase activity in females (19/22)^ref. High plasma cholesterol levels (9/11)^ref. High erythrocyte catalase level (1/18)^ref. Low intra-ocular pressure (4/4)^ref. High peripheral nerve conduction velocity (1/6)^ref. High brain L-glutamic acid decarboxylase (GAD) and choline acetyltransferase and catechol-O-methyltransferase (1/7 in all cases); low brain acetylcholinesterase (5/7) and monoamine oxidase activity (7/7)^ref. High brain tyrosine hydroxylase activity (1/5) (Ciranello et al., 1972., 1972). High brain plasmalogen (1/5)^ref. High proportion of time spent sleeping (1/6) with a high percentage of slow-wave sleep (2/6) and low proportion of paradoxical sleep (6/6)^ref. Short tau DD, the endogenous (free-running) period of the circadian pacemaker measured in constant environmental darkness (1/12)^ref. High hypoxanthene-guanine phosphoribosyl transferase in the thalamus (1/7)^ref. Low N-methylnicotinamide oxidase activity (5/7 males, 6/7 females)^ref. Low rectal (9/9) and tail (8/9) temperature^ref. High kidney arylsulphatase activity (2/12)^ref. Low basal level of serum prolactin (5/6)^ref. Low spermatazoal b-glucuronidase activity (8/9)^ref. Urine has high osmolality (1/7)^ref. High basal levels of kidney catalase (1/4), and superoxide dismutase (1/4) but low basal level of kidney glutathione peroxidase (4/4) and kidney glutathione (4/4)^ref. High level of alpha-fetoprotein in amniotic fluid and neonatal plasma (1/6)^ref. Low hepatic microsomal coumarin hydroxylase activity in males (8/8)^ref. Secretory group II phospholipase A2 gene has very high expression in small intestine (contrast 129/Sv and C57BL/6)^ref
Anatomy : large brain weight (1/18 in both sexes) (Storer, 1967), (2/25)^ref (1/6) (Wahlsten et al., 1975., 1975). Large brain to body weight ratio (2/20). Large spinal cord (5/25)^ref. Large relative kidney weight (2/21)^ref. Large forebrain (1/9) and hippocampus (1/9) volume^ref. Large number of A10 dopaminergic neurons in midbrain region (1/4) (Bernardini et al 1991). Corpus callosum absent in 39% of animals (1/6)^ref. This is associated with slow growth of the medial septum subadjacent to the cavum septi. See also strains I/LnJ and CXBG^ref. Absence of corpus callosum related to retarded formation of the hippocampal commissure in this strain and in 129/J mice^ref. Low bone density of femur^ref. Anatomy of Ammon's horn (hippocampus and dentate gyrus) different from that of 7 other strains^ref. High erythrocyte count (2/18 J substrain, 5/18 An substrain), high haematocrit (3/18 J substrain, 5/18 An substrain), high haemoglobin (1/18 J substrain, 4/18 An substrain)^ref. Large spleen at all ages (3/9 to 1/9)^ref. Accessory spleens in about 21% of animals, and number of nipples commonly exceeds 5 pairs (Hummel et al., 1966., 1966). Occasional (< 2%) cases of visceral inversion (Hummel and Chapman, 1959). Small pituitary^ref (5/6). Large proportion of sperm-head abnormalities (1/5, 44%)^ref. Low level of spontaneous sister chromatid exchange (1/4)^ref. Provides a sensitive and reproducible model of focal and global brain ischemia^ref.
Drugs : susceptible to skin ulceration by 7,12-dimethylbenz(a)anthracene (DMBA) (cf. 13/23)^ref. Sensitive to the development of uterine tumours following treatment with DMBA at 4-weeks of age (cf 3/6) (Tsubura et al, 1993). Sensitive to the induction of skin tumours by methylnitrosourea in methanol^ref. Susceptible to tumour induction by 3-methylcholanthrene (3/12)^ref. Susceptible to induction of leukaemia (1/6) but resistant (6/6) to induction of liver tumours by neonatally administered DMBA^ref. High incidence of interstitial tumours of testis induced by stilboestrol, high incidence of haemangioendotheliomas, particularly in interscapular fat pad and lung in mice treated with O-aminoazotoluene^ref. High incidence of lung tumours after administration of methycholanthrene by gavage (1/5) (Akamatsu and Barton, 1974). Injection of mineral oil i.p. induces a high incidence of transplantable plasmacytomas (myelomas). Bence Jones proteins include kappa and lamda light chains and the two-chain IgA protein. 60% of tumours are of the IgA type^ref. Susceptibility appears to be mediated by 2 genes on chromosome 4^ref. Susceptible (2/8) to daunomycin-induced nephrosis^ref. Sensitive to X-irradiation (26/27)^ref, (10/10) (Storer, 1966); low LD₅₀ to X-irradiation (9/9)^ref. Nicotine increases shock avoidance learning (3/9)^ref. Sensitive to insulin (3/9)^ref. Poor ovulatory response to PMS at both 3 IU (6/6) and 7 IU (5/6), but response increased by exposure to males^ref. Low locomotor excitation after treatment with D-amphetamine (6/6)^ref. Resistant to hyperbaric oxygen (16/18)^ref. Insensitive (eosinophil response) to cortisone acetate (cf. 3/6)^ref. Low sensitivity to induction of malformed ribs and vertebrae by hypoxia on ninth day of gestation (5/5) (Dagg, 1966). Sensitive to chloroform toxicity (cf. 5/10) (Christensen et al., 1963., 1963). Resistant to toxic effects of isoniazid (1/10) (Taylor, 1976b). Resistant (3/3) to neurotoxic effects of monocrotophos^ref. High transient increase in renal lipid peroxidation following treatment with nickel (1/4)^ref. Resistant to biliary tract injury following oral dosing with 500 mg of the fungal toxin sporidesmin (3/4), but the injury is much more persistent than in SJL and was accompanied by periductal fibrosis and occasionally by obliteration of ducts typical of sclerosing cholangitis^ref. High LD₅₀ following injection of butylated hydroxytoluene (BHT) (1/4)^ref. High histamine release from peritoneal mast cells induced by compound 48/80, a calcium dependent histamine releaser (1/8)^ref. High histamine release from peritoneal mast cells induced by Ca²⁺ ionophore A23187 ( c.f. 7/8, contrast C57BL/6)^ref. Cultured mast cells grow more slowly and release less histamine and TNF-a following anti-DBN IgE antibody treatment than those of strain SJL^ref. Highly sensitive to the induction of catalepsy by haloperidol (1/8) associated with midbrain dopamine D₂ receptor density levels^ref. Resistant to both acute and chronic cadmium toxicity (contrast NFS) (Abshire and Waalkes, 1994). However, cadmium can induce hematopoetic and suppress pulmonary tumours in these mice (Waalkes and Rehm, 1994). Resistant to weight loss induced by cocaine (1/7)^ref. Clonidene induces a strong aggressive behavioural response (1/9)^ref. More resistant to acute toxic effects of aflatoxin B-1 than C57BL/6^ref. The IgE response following topical application has been used to predict which chemicals may have the potential to cause sensitization of the respiratory tract^ref. More susceptible to the development of micronuclei than C57BL/6 or DBA/2 following treatment with clastogenic base analogues and nucleosides^ref. Estrogen does not induce an increase in VLDL and LDL-cholesterol (like C3H contrast C57BL/6 and C57L))^ref.
Immunology : genetic bias to T_h2 responses; resistant to experimental allergic encephalomyelitis (EAE) (cf. 7/18)^ref. Resistant to EAE (9/10) with short duration (10/10) but moderate mortality^ref. High lymphocyte phytohaemagglutinin response (14/43)^ref. Good immune response to type III pneumococcal polysaccharide (1/5)^ref. Good splenic PFC immune response to pneumococcal polysaccharide (1/9)^ref. Poor primary immune response to bacteriophage fd (7/7 in Str substrain, 5/7 in Ho substrain)^ref. Poor immune response to synthetic dsRNA (7/7)^ref. Responder to synthetic polypeptide (cf. 3/7)^ref and Glu⁶⁰, Ala³⁰, Tyr¹⁰ (2/10)^ref. Very good immune response to cholera A and B antigens (1/9)^ref. Good immune response to dextran -1,3-glucosyl linkages (cf. 4/10)^ref. Good primary immune haemolysin and haemagglutinin response (1/6 at various dose levels)^ref. Poor immune response to Salmonella anatum and S. senftenberg (5/5)^ref and Salmonella strasbourg (6/7)^ref LPS. Good immune response to Vi antigen (1/5) (Gaines et al., 1965., 1965). Precipitating and skin-sensitising antibodies have fast electrophoretic mobility (1/6)^ref. Non-discriminator between `H' and `L' sheep RBC (cf. 6/18)^ref. Low anti-DNP antibody concentration (6/7)^ref. High PHA-stimulated lymphocyte blastogenic response (1/6)^ref. Erythrocytes have a low agglutinability (cf. 11/25)^ref. High responder to dextran (cf. 4/10)^ref. Resistant to induction of experimental autoimmune thyroiditis (cf. 2/5) (Vladutiu and Rose, 1971a). Resistant (5/5) to induction of autoimmune prostatitis (contrast C57BL/6)^ref. Immunization by intraperitoneal injection of fetal human (but not calf) proteoglycan depleted of chondroitin sulphate together with complete or incomplete Freund's adjuvant produces progressive polyarthritis and ankylosing spondylitis. Clinical assessment suggests that affected mice have many similarities to human rheumatoid arthritis and ankylosing spondylitis. Eventually, the joints become stiff and deformed. Antibodies against collagen type II were detected in approximately 25% of arthritic mice, but only following cartilage degradation. Sublines differed in their response, but 9 other mouse strains and 5 F₁ hybrids were resistant. Resistant to induction of anaphylactic shock by ovalbumin (cf. 6/13) (Tanioka and Esaki, 1971). Anti-BPO IgE monoclonal antibody failed to produce potent systemic sensitization sufficient for provocation of lethal shock in most aged (6 to 10 months) mice (c.f. 5/8)^ref. Low immunological response to Salmonella typhi porins (4/4) (Gonzales et al, 1995). Resistant to immunosuppression of contact hypersensitivity by UVB light (cf 4/18)^ref. Low neutrophil response to thioglycolate broth and killed bacteria (contrast C57BL/10)^ref. Pristane induces immune complex glomerulonephritis in association with autoantibodies typical of lupus erythematosus, though the strain is not normally considered to be susceptible to the disease^ref. The IgE response following topical application has been used to predict which chemicals may have the potential to cause sensitization of the respiratory tract^ref. Diminished expression of neutral glycosphingolipid GgOse(4)Cer in concanavalin A stimulated T lymphoblasts (cf 3/6) ^ref
Infection : highly susceptible to infection by Salmonella typhimurium strain C5 (1/7)^ref, (2/5) (Robson and Vas, 1972). Relatively resistant to a natural intestinal helminth infection (1/10)^ref. High susceptibility to BALB/Tennant leukaemia virus (1/12)^ref. Transmission of murine leukaemia virus (Scripps) through 3 successive generations 100% (cf. 2/5)^ref. Highly susceptible to development of leukaemia on infection with Friend virus (cf. 5/11)^ref. Susceptible to Mycobacterium marinum (3/9) and good plateau harvest of M. leprae 8 months after infection (2/9)^ref. Susceptible to infection with Mycobacterium paratuberculosis, and develops a chronic infection^ref. Susceptible to infection with Mycobacterium avium, but resistance is enhanced by Freund's incomplete adjuvant^ref. Susceptible to infection with Yersinia enterocolitica associate with a poor IFN-g response (contrast C57BL/6)^ref. Susceptible to the induction of chronic pyelonephritis with Escherichia coli after introduction of the bacteria by the ascending route^ref. Relatively resistant to infection with Helicobacter felis (contrast C57BL/6)^ref. Resistant to infection by Helicobacter felis with only mild gastritis in the antrum and no atrophy seen over time (cf CBA, contrast 4 other strains)^ref. Susceptible to mouse hepatitis virus type 3 (cf. 5/14)^ref. Resistant to mouse adenovirus type 1 (contrast C57BL/6)^ref. Resistant to induction of diabetes mellitus by encephalomyocarditis virus (cf. 7/14)^{ref1, ref2}. Resistant to measles virus induced encephalitis, which correlates with a low CTL response (contrast C3H, C57BL/6)^ref. Highly susceptible to the Leishmania tropica parasite, with the local disease being uncontrolled and with the development of metastases and fatal visceralization^ref. Supported sustained growth of 6 strains of Leishmania mexicana mexicana (contrast C57BL/6)^ref. Highly susceptible to Leishmania major, with the parasites disseminated within 10-24 hrs. from the site of subcutaneous footpad injection into the popliteal lymph node, spleen, lung, liver and bone marrow in contrast to resistant C57BL/6, CBA/J and C3H/HeJ^ref. Susceptible (1/4) to infection with the helminth worm Angiostrongylus costaricensis^ref. Susceptible (6/7) to the induction of dental caries due to infection with Streptococcus mutans^ref. Resistant to infection with Pseudomonas aeruginosa in contrast with susceptible DBA/2 mice. Resistance is associated with a quicker inflammatory response and earlier initiation of bacterial clearance^ref. Develop mycotic mastitis following inoculation of the mammary gland with Candida krusei isolated from bovine mastitis^ref. Susceptible (1/7) to the development of chronic Chagas' cardiomyopathy in postacute Trypanosoma cruzi infection^ref. Susceptible to infection with Trypanosoma congolense with unrestrained parasite growth to the time of death about 12 days later (contrast C57BL/6)^ref. Resistant to lethal and body weight effects of Toxacara canis, but high larval brain levels (1/5)^ref. Infection with larval Echinococcus multilocularis by transportal injection of hydatid homogenate results in a multivesiculation form of hyatid development (cf 4/9)^ref. Susceptible to Streptococcus suis type 2 including the type strain, 2 isolates from meningitis in pigs and 2 isolates from tonsils of clinically healthy pigs (c.f. 2/5)^ref. Resistant to street rabies virus (SRV) injected via the intraperitoneal route^ref. Following administration of murine cytomegalovirus, BALB/c, BALB.B, and BALB.K mice develop persistent myocarditis regardless of age at infection, and age-related cardiopathy is frequent and severe in infected and uninfected mice (contrast C57BL/10 and C3H)^ref. Susceptible to the lethal effects of murine hepatitis virus strain 3 (contrast A/J)^ref. The mouse hepatitis virus JHM strain induces a biphasic retinal disease^ref (Wang et al, 1996). Susceptible to infection with the tick-born Thogoto virus, with severe symptoms and death after a few days. The congenic strain carrying the Mx1 gene from strain A2G is resistant^ref. Susceptible to herpes simplex virus-1 (contrast C67BL/6)^ref. Develop carditis on infection with Lyme borreliosis (Borrelia burgdorferi)^ref, but develop only mild arthritis (contrast C3H/HeJ)^ref. Hepatic amoebiasis can be induced by introducing Entamoeba histolytica-infected hamster liver tissue in between the adjacent liver lobes of these mice^ref. Resistant to intra-vaginally innoculated Neisseria gonorrhoeae (c.f. 5/5)^ref. Susceptible (2/10) to infection with Ehrlichia risticii^ref. Widely used in study of Plasmodium berghei infections, though much less sensitive than C57BL/6^ref. Infection with P. berghei results in high peripheral blood parasitemia and death within 22-24 days, but without neuological complication, in contrast with the more susceptible C57BL/6^ref. Susceptible (1/4) to disseminated Cryptococcus neoformans^ref. Nippostrongylus brasiliensis normally rejected by 14 days postinfection. However, this pattern of self-cure was not observed in a "putative" BALB/c substrain from the University of Texas^ref. Susceptible, with high amylase response to the fungus Paracoccidioides brasiliensis (cf 6/12)^ref. Susceptible to the protozoan parasite Neospora canium following subcutaneous inoculation with tachyzoites of the NC-1 strain^ref. May develop mite-associated ulcerative dermatitis with an allergic reaction to parasite-derived substances following infection with Mycoptes musculinus^ref
Reproduction : good breeding performance (8/25). Colony output 1.18 young/female/wk, litter size at weaning 5.2 (15/25)^ref. Good breeding performance, mean 3.24 young/female/month (1/24) (Hansen et al., 1973). Intermediate breeding performance (5/8), litter size 5.1 _ 0.3, sterility 32%^ref. Low litter size (6/6)^ref. Low pre-implantation loss of embryos (1/8), but high post-implantation losses (8/8) (Leonard et al., 1971., 1971). Embryos subject to the 2-cell block and only grow successfully in culture from the late 2-cell stage^ref.
Miscellaneous : recommended host for transplantable tumours: melanoma HP and pleomorphic sarcoma 5180 (although the latter is not host-specific) (Kaliss, 1972). Low mortality after neonatal thymectomy (2/6)^ref. Embryonic stem cell lines have been established^ref
See also murine immune system and transmissible and nontrasmissible diseases carried by mice
2 types of Purina Mills LabDiet, a leading brand of rodent chow, contain markedly different amounts of isoflavones, a family of molecules common in food plants such as soy and alfalfa and that can simulate estrogen. Mice at Vanderbilt typically eat the high-isoflavone Purina mix, while those at Kansas were fed another variety. Mice on the high-isoflavone diet had strikingly heavier wombs (more than 40% heavier by "wet weight" on a scale) than the animals that ate the other food. Their uterine cells also showed different patterns of gene expression, particularly among those involved in the response to estrogen. And, their blastocysts implanted faster^ref. How that might affect offspring is unclear, though it's not necessarily serious. On the other hand, you don't want to play with this normal window. Each of the effects Dey's group uncovered could influence studies designed to measure the impact of plant estrogens (phytoestrogens) on rodents, and by implication, on people. Some evidence suggests that phytoestrogens and synthetic estrogens, both of which can bind to estrogen receptors and thus mimic the human sex hormone, can cause reproductive complications in people, especially young children. Phytoestrogens are typically weaker than human estrogens. Moreover, phytoestrogens can in some cases block the human hormone by preventing it from meeting its proper receptors. So it is perfectly understandable that the presence or absence of these phytoestrogens could have an effect in rodent studies that are examining outcomes that are responsive to estrogens. While the health effects for mice of eating plant estrogens are not clear, the amount of the chemicals in lab chow should probably be standardized for the sake of consistent research. Indeed, the National Institute of Environmental Health Sciences is sponsoring a "brainstorming session" in September 2005 to examine the effects of diet on animals used in toxicology and endocrine experiments.
Web resources :
• The PHL Murine Immunohistochemistry Database
• Mouse Pathology Lab Protocols by Giorgio Cattoretti, MD, Columbia University
• Mouse Models of Human Cancers Consortium
• The Mouse Atlas (3D embryos at different developmental stage) and Gene Expression Database Project from the the Medical Research Council and University of Edinburgh
• European Mouse Mutant Archive (EMMA)
• Rattus norvegicus (Norway rat) (genome sequencing projects). See also transmissible and nontrasmissible diseases carried by Norway rat.

Roll of honour :
• fifth to fifteenth century : global domination
• 1621 : sexual confusion
• early nineteenth century : into the lab
• 1856 : colonization
• 1877 : well bred
• 1900 : model behaviour
• 1906 : setting the standard
• 1920 : cancer research
• 1963 : under pressure
• 1971 : short of breath
• 1980 : in the swim
• 1980s : spare part surgery
• 2002 : remote control
• 2003 : seeing double

Rats would have a ‘better’ life in the lab if provided with a more natural environment. Cages can be made more like a field by adding sticks to gnaw on and tunnels to run through, but such environmental enrichment appears to compromise the results of experiments. A complex cage tends to produce more individualised animals that have a broader range of behaviour and that broad range makes it more difficult to distinguish between control and experimental groups or discern trends in behaviour. To avoid this, researchers would have to use larger numbers of animals and that introduces an interesting moral dilemma – is it better to cage fewer rats in poor welfare conditions, or many more rats in a better environment?
Web resources :
• The Laboratory Rat: A Natural History : a documentary film that proves that 75 docile laboratory rats that hasn't been outside a lab for 200 generations can still survive in the wild into an Oxfordshire farmyard
• Jackson Hole: Wildlife Film Festival
• Rat Community Forum
• Rat Behaviour and Biology
• Rattus rattus (black rat) also is used as an experimental model, but has not contributed to the common laboratory rat strains. See also transmissible and nontrasmissible diseases carried by black rat.


• Gnathostomata (jawed vertebrates); Teleostomi; Euteleostomi;
• Actinopterygii; Actinopteri; Neopterygii; Teleostei; Elopocephala; Clupeocephala
• Euteleostei; Neognathi; Neoteleostei; Eurypterygii; Ctenosquamata; Acanthomorpha; Euacanthomorpha; Holacanthopterygii; Acanthopterygii; Euacanthopterygii; Percomorpha
• Smegmamorpha; Atherinomorpha; Beloniformes; Adrianichthyoidei; Adrianichthyidae; Oryziinae; Oryzias
• Oryzias latipes (Japanese medaka or rice fish)^ref


• Tetraodontiformes; Tetraodontoidei; Tetradontoidea; Tetraodontidae; Takifugu
• Takifugu rubripes (a.k.a. torafugu, puffer-fish, previously called Fugu rubripes)


• Otocephala; Ostariophysi; Otophysi; Cypriniphysi; Cypriniformes; Cyprinoidea; Cyprinidae; Rasborinae; Danio
• Danio rerio (a.k.a. Brachydanio rerio, zebrafish, zebra danio) (genome sequencing projects)


• Sarcopterygii; Tetrapoda
• Amniota
• Mammalia; Theria; Eutheria; Rodentia
• Hystricognathi; Caviidae; Cavia
• Cavia porcellus (a.k.a. Cavia cobaya, Cavia aperea porcellus, Cavia cobya, domestic guinea pig). See also transmissible and nontrasmissible diseases carried by guinea pig.


• Sciurognathi; Muridae
• Cricetinae(hamsters)
• Murinae; Rattus
• Sauropsida; Sauria; Archosauria; Aves; Neognathae
• Galliformes
• Odontophoridae(American quails)
• Psittaciformes; Psittacidae; Melopsittacus
• Melopsittacus undulatus (a.k.a. Melopsittacus unduratus, budgerigar / budgie [Australian aboriginal gijirrigaa]) : a species of parakeet, native to Australia, popular as a cage pet and used for experimental work in psittacosis
• Amphibia; Batrachia; Anura; Mesobatrachia; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus
• Xenopus laevis (toad) (genome sequencing projects)


Web resources : Embryogenesis : Xenopus laevis
• Panarthropoda; Arthropoda; Mandibulata; Pancrustacea; Hexapoda; Insecta; Dicondylia; Pterygota; Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Schizophora; Acalyptratae; Ephydroidea; Drosophilidae; Drosophilinae; Drosophilini; Drosophilina; Drosophiliti; Drosophila; Sophophora; melanogaster group
• melanogaster subgroup
• Drosophila melanogaster (fruitfly) (genome sequencing projects)


Web resources : The Virtual Transgenic Fly Lab
• montium subgroup
• Drosophila serrata
Web resources : The Interactive Fly : Drosophila melanogaster embryogenesis
• Echinodermata; Eleutherozoa; Echinozoa; Echinoidea; Euechinoidea; Echinacea; Arbacoida; Arbaciidae; Arbacia
• Arbacia punctulata (punctuate or purple-spined sea urchin) : classical subject of embryological studies


Phenomenological aspects of endomesoderm specification in sea urchin embryos : developmental process
• autonomous cues of materal origin
• nuclearization of b-catenin in micromeres (by fourth cleavage) and veg₂ cells (from sixth cleavage on)
• exclusion of ectodermal transcription factors from vegetal-most cell nuceli
• nuclearization of Otx factor in micromeres at fourth cleavage
• early micromere signal : micromere signal to veg₂ (fourth through sixth cleavage) required for normal endomesodermal specification
• Wnt8/Tcf loop
• Wnt8 ligand expressed throughout endomesodermal domain maintains and strengthens b-catenin/Tcf input in these nuclei
• b-catenin/Tcf input required for endomesoderm specification
• late micromer signal
• expression of Delta ligand in micromeres
• activation of Notch signal transduction in veg₂ descendants adjacent to micromeres that receive Delta signal
• skeletogenesis : skeletogenic functions expressed after ingression of skeletogenic cells in late blastula
• specification of veg₂ mesoderm and endoderm
• segregation of cell type precursors within vegetal plate complete by late blastula
• mesoderm cells turn off endoderm genes, leaving endoderm genes expressed in peripheral veg₂ cells
• sepcification of veg₁ endoderm : Wnt8 signal from veg₂ to veg₁ and activation of b-catenin nuclearization in abutting veg₁ cells
• invagination of archenteron
• veg₂ mesoderm carried inward at tip of archenteron on gastrulation
• followed by roll-in of veg₁ endoderm, contributing mainly hindgut
• Protostomia
• Mollusca
• Cephalopoda; Coleoidea; Neocoleoidea; Decapodiformes;
• Loliginidae; Loligo
• Loligo pealei (a.k.a. longfin inshore squid) : subject of studies of nerve function because of its giant axon (nearly 1 mm diameter, roughly a thousand times larger than typical mammalian axons)


• Oegopsida; Architeuthidae
• Architeuthis princeps (a.k.a. longfin inshore squid)
• Gastropoda; Orthogastropoda; Apogastropoda; Heterobranchia; Euthyneura; Opisthobranchia; Anaspidea; Aplysioidea; Aplysiidae; Aplysia
• Aplysia californica (a.k.a. California sea hare)

• Caenorhabditis elegans (a.k.a. roundworm) (genome sequencing projects) : 959 cells

• (standard) inbred strains :
• brother x sister mating for > 20 consecutive generations : and individuals of the strain can be traced to a single ancestral pair at the 20^th or subsequent generation. At this point the individuals' genomes will on average have only 0.01 residual heterozygosity (excluding any genetic drift) and can be regarded for most purposes as genetically identical. Inbred strains must be continuously mated brother x sister (or equivalent) thereafter.
• parent x offspring mating for > 20 consecutive generations, provided that the younger of the parents is always used (i.e., the offspring that is mated to parent is subsequently mated to its offspring).
• other breeding schemes are acceptable provided that the inbreeding is equivalent to 20 successive generations of sib mating
Inbred strains that have a common origin, but separated before F20, are related inbred strains, and symbols [e.g. (F _ ) or (F?+ _)] should reflect this relationship.
Established inbred strains may genetically diverge with time into substrains if ...
• 2 branches are separated after 20 but before 40 generations of inbreeding, there will still be enough residual heterozygosity that 2 genetically different substrains will result
• branches are separated for > 20 generations from a common ancestor, it is likely that genetic variation between the branches will have occurred by mutation and genetic drift.
• genetic differences are proven by genetic analysis to have occurred between branches.
Substrains are given the root symbol of the original strain, followed by a forward slash and a substrain designation (but BALB/c is not a substrain !).
• hybrids : mice or rats that are the progeny of 2 inbred strains, crossed in the same direction, are genetically identical, and can be designated using upper case abbreviations of the two parents (maternal strain listed first), followed by F1. Further crosses produce offspring that are no longer genetically identical, but it may still be appropriate to give them designations reflecting their parentage.
• strains made from multiple inbred strains
• recombinant inbred (RI) strains are formed by crossing 2 inbred strains, followed by > 20 consecutive generations of brother x sister mating. These strains should be designated by upper case 1- or 2-letter abbreviations of both parental strain names, with the female strain written first, and separated by an upper case letter X with no intervening spaces.
• mixed inbred strains : incipient inbred stocks or inbred strains that are derived from only 2 parental strains (one of which could be a gene-targeted ES cell line) can be designated using upper case abbreviations for the 2 strains, separated by a semicolon
• recombinant congenic (RC) strains are formed by crossing 2 inbred strains, followed by a few (usually 2) backcrosses of the hybrids to one of the parental strains (the "recipient" strain), with subsequent inbreeding without selection for any specific markers. Such inbred strains will consist of the background recipient strain genome interspersed with homozygous segments of the donor (the amount of donor strain genome depending on the number of original backcrosses, 2 backcrosses will give on average 12.5%). 1 generation of backcrossing will be regarded as being equivalent to 2 generations of brother x sister mating.
• advanced intercross lines (AIL) are made by producing an F2 generation between 2 inbred strains and then intercrossing in each subsequent generation, but avoiding sibling matings. The purpose is to increase the possibility of tightly linked genes recombining.

• coisogenic strains are inbred strains that differ at only 1 single locus through mutation occurring in that strain. Strains containing targeted mutations in ES cells that are then crossed to, and maintained, on the same inbred substrain from which the ES cells were derived can be regarded as coisogenic, but the possibility of mutations elsewhere should be considered. Similarly, chemically or radiation induced mutants on an inbred background can be considered coisogenic, although other genomic alterations could be present. A coisogenic strain may accumulate genetic differences over time by genetic drift unless periodically backcrossed to the parental strain.
• congenic (Cg) strains are produced by > 10 backcrosses (counting the first hybrid or F1 generation as generation 1) to an inbred (background) strain, with selection for a particular marker from the donor strain. At this point the residual amount of unlinked donor genome in the strain is likely to be < 0.01 (note that the amount of donor genome linked to the selected gene or marker is reduced at a much slower rate, approximately equivalent to 200/N, where N is the number of backcross generations for N>5)
• congenic resistant (CR) strains : congenic lines that differ at a histocompatibility locus and therefore resist each other's grafts
• speed congenics : marker assisted breeding or marker assisted selection breeding permits the production of congenic strains equivalent to 10 backcross generations in as few as 5 generations. Descriptions of speed congenic strains in first publications thereof should include the number and genomic spacing of markers used to define the congenicity of the strain
• consomic strains / chromosome substitution strains are produced by > 10 backcrossings (counting the first hybrid or F1 generation as generation 1) of a whole chromosome onto an inbred strain.  For autosomes, it is necessary to genotype progeny to ensure that the selected donor chromosome has not recombined with the corresponding recipient chromosome. The generic designation for consomic strains is HOST STRAIN–CHROMOSOME^{DONOR STRAIN}.
• segregating inbred strains are inbred stains in which a particular allele or mutation is maintained in heterozygous state. They are developed by inbreeding (usually brother x sister mating) but with heterozygosity selected at each generation.
• conplastic strains are strains in which the nuclear genome from one strain has been crossed onto the cytoplasm of another, i.e., the mitochondrial donor is always the female parent during the backcrossing program. The designation is NUCLEAR GENOME–mt^{CYTOPLASMIC GENOME}.

• Council Directive 86/609/EEC of 24 November 1986 on the approximation of laws, regulations and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes
• Netherlands Centre Alternatives to Animal Use
• Rules for Nomenclature of Mouse and Rat Strains at Mouse Genome Informatics

• Neurospora crassa
• baker's yeast (Saccharomyces cerevisiae) (genome sequencing projects)
• fission yeast (Schizosaccharomyces pombe)

• thale cress (Arabidopsis thaliana) (genome sequencing projects)
• Chlamydomonas reinhardtii
• rice (Oryza sativa)
• maize (Zea mays)

• slime mould (Dictyostelium discoideum) (genome sequencing projects)

Web resources : dictyBase

• Tetrahymena thermophila

• Escherichia coli
• Mycoplasma genitalium

• negative control : a laboratory procedure identical in all respects to an experimental procedure except for the absence of the one factor being studied
• positive control : in an experimental study of a given substance, a sample of the substance with known values that can be used as a reference base.

• conventional animal : an experimental animal that has not been reared under gnotobiotic conditions.
• holoxenic : raised under usual circumstances; said of an animal not raised under special laboratory conditions, as opposed to one raised in a germ-free environment
• gnotobiotic animals are animals who are achived by gnotobiotics : the science of raising (gnotophoresis) laboratory animals (gnotobiote) whose microfauna and microflora (gnotobiota) are specifically known in their entirety.
• germ-free (GF) / axenic : not contaminated by or associated with any foreign organisms
• specified pathogen-free (SPF) animals are germ-free from a given pathogen only.
• all contaminating species are known
• parabiotic animals : parabiosis is the union of 2 individuals, as of conjoined twins or of experimental animals by surgical operation.
• cross circulation : the circulation in a portion of the body of one animal of blood supplied from another animal
• dialytic parabiosis : the circulation of the blood of 2 individuals through a dialyzer, separated by a membrane which permits the removal of harmful material from the recipient's blood and the contribution of essential factors from the donor's blood.
• vascular parabiosis : the crossing of the circulation between 2 individuals by anastomosis of blood vessels.
• thalamic animal : an animal in which the brain stem has been transected just above the thalamus.
• decerebrate animal : an experimental animal that has been subjected to decerebration; such an animal exhibits rigid extension of the legs, with strong tonic contraction of the extensor muscles and to some extent the flexor muscles
• spinal animal : an animal whose spinal cord has been severed, thus cutting off communication with the brain
• Houssay animal : an experimental animal deprived of both pituitary gland and pancreas
• hyperphagic animal : an experimental animal in which the cells of the ventromedial nucleus of the hypothalamus have been destroyed, abolishing its awareness of the point at which it should stop eating; excessive eating and savageness characterize such an animal.
• Long-Lukens animal : an experimental animal which has been deprived of the pancreas and adrenal glands.
• nuclein animal : an animal into which a certain amount of nuclein has been injected.

• halothane inhalation
• CO₂ inhalation
• intraperitoneal sodium pentobarbital
• intravenous potassium chloride (KCl: 330 mg/ml) (e.g. in hamsters^ref)
• cervical dislocation with and without anesthesia.

Lisa Wiesmüller, 43, head of gynecological oncology at the University of Ulm, was honored for developing a test using human cell culture to detect potential carcinogenic effects or genetic damage from medicines and food additives. Such testing currently requires use of animals. They won the 2004 Ursula M. Händel Animal Protection Prize given by the German Research Foundation (DFG). Klaus Otto, 51, professor of experimental surgery and anesthesiology at the central animal laboratory of the University of Hanover's Medical School was recognized for his work to find more accurate means of measuring the effectiveness of general anesthesia on animals used in research. Instead of using traditional measuring methods such as heart rate, blood pressure, and pupil dilation, he used electroencephalogram to measure brain activity

• animal rights extremism or terrorism
• in 2004, the activities of animal rights groups have been credited with the scrapping of plans for a multimillion-pound primate lab for research on neurological condition in Cambridge^ref and the suspension of work on a new £18-million ($34-million) animal house in Oxford^ref. The measures to defend against extremist acts cost the United Kingdom's universities about £175,000 each per year
• animal rights activists who disrupt UK medical research could face up to 5 years in jail, if a legal amendment proposed on 31 January 2005 by the British government becomes law. The new law would make it a criminal offence to cause "economic damage" to businesses connected with animal research, either by intimidating individuals or by interfering with commercial activities. Current legislation focuses on physical damage caused by protestors. But activists are increasingly trying to undermine animal-testing laboratories by targeting the companies that supply them, even threatening courier services who make deliveries to the high-security sites. The amendment is part of the Serious Organised Crime and Police bill^ref, which will be voted on by the UK parliament in the coming months. If successful, the bill would become law around October 2005. The bill, first presented to the House of Commons on 24 November 2004, already includes measures to prevent protestors gathering outside people's homes if it is likely to cause residents "alarm or distress". Campaigners in the United States are urging their government to introduce similar laws. The US Animal Enterprise Protection Act was passed in 1992 to discourage the disruption of commercial activities using animals. Animal rights activism has grown in the United States in the past decade. Britain has a long history of animal-rights activism. In the past decade, supporters of animal research have been attacked with baseball bats and had letter bombs delivered to their homes. Economic harassment has become increasingly common in recent years.
Web resources :
• Home Office: Animals in Scientific Procedures
• pro-animal research
• Victims of Animal Rights Extremism (VARE)
• Research Defence Society (RDS)
• National Association for Biomedical Research (NABR)
• Coalition for Medical Progress
• Association of Medical Research Charities (AMRC)
• against-animal research
• American Anti-Vivisection Society (AAVS)
• Animal rights 2004
• British Union for the Abolition of Vivisection (BUAV)
• People for the Ethical Treatment of Animals (PETA)
• SPEAK
• SPEAC (Stop Primate Experiments at Cambridge)
• Stop Huntingdon Animal Cruelty (SHAC)
• Save British Science
• Uncaged Campaigns

• Associations (see also Italian associations) :
• American Association for Accreditation of Laboratory Animal Care (AAALAC)
• Association Française des Sciences et Techniques de l'Animal de Laboratoire (AFSTAL)
• European Society of Laboratory Animal Veterinarians (ESLAV)
• Institute of Laboratory Animal Resources Commission on Life Sciences National Research Council 1996
• Laboratory Animal Sciences Program (LASP) at Center for Cancer Research (CRC), NCI Frederick
• The Virtual Library - Model Organisms
• Model organisms at NIH
• Model organisms resources

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