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57-718: The MGI resource was first published online in 1994 and is a collection of data, tools, and analyses created and tailored for use in the laboratory mouse , a widely used model organism . It is "the authoritative source of official names for mouse genes, alleles, and strains", which follow the guidelines established by the International Committee on Standardized Genetic Nomenclature for Mice. The history and focus of Jackson Laboratory research and production facilities generates tremendous knowledge and depth which researchers can mine to advance their research. A dedicated community of mouse researchers, worldwide enhances and contributes to

114-518: A 2014 study from McGill University which suggests that mice handled by men rather than women showed higher stress levels. Another study in 2016 suggested that gut microbiomes in mice may have an impact upon scientific research. The worldwide market for gene-altered mice is predicted to grow to $ 1.59 billion by 2022, growing at a rate of 7.5 percent per year. Taxonomy Lucien Cu%C3%A9not Lucien Claude Marie Julien Cuénot ( French: [keno] ; 21 October 1866 – 7 January 1951)

171-484: A Mendelian fashion. Subsequently, Cuénot was the first person to describe multiple allelism at a genetic locus . He also described a lethal mutation in the mouse agouti locus at a time when such a mutation was unheard of. There is some argument over the degree of recognition of Cuénot's pioneering work in his own day, and up until the present. Some scientists who were famous in Cuénot's day such as William Bateson ,

228-556: A dark brown, nearly black coat. They are more sensitive to noise and odours and are more likely to bite than the more docile laboratory strains such as BALB/c . Group-housed C57BL/6 mice (and other strains) display barbering behaviour, which used to be seen as a sign of dominance. However, it is now known that this is more of a stereotypical behaviour triggered by stress, comparable to trichotillomania in humans or feather plucking in parrots. Mice that have been barbered extensively can have large bald patches on their bodies, commonly around

285-447: A good model for early-stage AD because they show amyloidogenesis and working memory impairments linked to age but do not show neuronal degeneration. The absence of cell death suggests that changes in typical cellular signaling cascades involved in learning and synaptic plasticity are probably linked to the memory phenotype. Associative learning impairments are exacerbated when Tg2576 mice are crossed with PS1 transgenic animals that possess

342-463: A lower neutrophil enzymatic capacity, lower activity of the complement system , and a different set of pentraxins involved in the inflammatory process ; and lack genes for important components of the immune system, such as IL-8 , IL-37 , TLR10 , ICAM-3 , etc. Laboratory mice reared in specific-pathogen-free (SPF) conditions usually have a rather immature immune system with a deficit of memory T cells . These mice may have limited diversity of

399-405: A number of researchers. Regarding experiments on mice, some researchers have complained that "years and billions of dollars have been wasted following false leads" as a result of a preoccupation with the use of these animals in studies. Mice differ from humans in several immune properties: mice are more resistant to some toxins than humans; have a lower total neutrophil fraction in the blood ,

456-535: A single breeding pair. Inbred mice have several traits that make them ideal for research purposes. They are isogenic , meaning that all animals are nearly genetically identical. Approximately 98.7% of the genetic loci in the genome are homozygous , so there are probably no "hidden" recessive traits that could cause problems. They also have very unified phenotypes due to this stability. Many inbred strains have well documented traits that make them ideal for specific types of research. The following table shows

513-616: A standard for their care and use. Compliance with the PHS is required for a research project to receive federal funding. PHS policy is administered by the Office of Laboratory Animal Welfare. Many academic research institutes seek accreditation voluntarily, often through the Association for Assessment and Accreditation of Laboratory Animal Care , which maintains the standards of care found within The Guide for

570-525: A tunnel or cupped hands is advocated. In behavioural tests, tail-handled mice show less willingness to explore and to investigate test stimuli, as opposed to tunnel-handled mice which readily explore and show robust responses to test stimuli. In nature, mice are usually herbivores , consuming a wide range of fruit or grain. However, in laboratory studies it is usually necessary to avoid biological variation and to achieve this, laboratory mice are almost always fed only commercial pelleted mouse feed. Food intake

627-632: Is 20 days. A fertile postpartum estrus occurs 14–24 hours following parturition , and simultaneous lactation and gestation prolongs gestation by 3–10 days owing to delayed implantation. The average litter size is 10–12 during optimum production, but is highly strain-dependent. As a general rule, inbred mice tend to have longer gestation periods and smaller litters than outbred and hybrid mice. The young are called pups and weigh 0.5–1.5 g (0.018–0.053 oz) at birth, are hairless, and have closed eyelids and ears. Pups are weaned at 3 weeks of age when they weigh about 10–12 g (0.35–0.42 oz). If

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684-430: Is a group in which all members are as nearly as possible genetically identical. In laboratory mice, this is accomplished through inbreeding . By having this type of population, it is possible to conduct experiments on the roles of genes, or conduct experiments that exclude genetic variation as a factor. In contrast, outbred populations are used when identical genotypes are unnecessary or a population with genetic variation

741-518: Is a small mammal of the order Rodentia which is bred and used for scientific research or feeders for certain pets. Laboratory mice are usually of the species Mus musculus . They are the most commonly used mammalian research model and are used for research in genetics , physiology , psychology , medicine and other scientific disciplines . Mice belong to the Euarchontoglires clade, which includes humans . This close relationship,

798-410: Is also possible. Each route has a recommended injection site, approximate needle gauge and recommended maximum injected volume at a single time at one site, as given in the table below: To facilitate intravenous injection into the tail, laboratory mice can be carefully warmed under heat lamps to vasodilate the vessels. A common regimen for general anesthesia for the house mouse is ketamine (in

855-630: Is an NHGRI -funded project which contributes to the Mouse Genome Informatics database. The Gene Expression Database is a community resource of mouse developmental expression information. MGI evolved from a project funded by the National Center for Human Genome Research in 1989 to combine the databases of several Jackson Laboratory scientists and create a tool for visualizing data on the mouse genome. The result of that project, led by Joseph H. Nadeau, Larry E. Mobraaten, and Janan T. Eppig,

912-531: Is an albino laboratory-bred strain from which a number of common substrains are derived. With over 200 generations bred since 1920, BALB/c mice are distributed globally and are among the most widely used inbred strains used in animal experimentation . BALB/c are noted for displaying high levels of anxiety and for being relatively resistant to diet-induced atherosclerosis , making them a useful model for cardiovascular research. Male BALB/c mice are aggressive and will fight other males if housed together. However,

969-465: Is approximately 15 g (0.53 oz) per 100 g (3.5 oz) of body weight per day; water intake is approximately 15 ml (0.53 imp fl oz; 0.51 US fl oz) per 100 g of body weight per day. Routes of administration of injections in laboratory mice are mainly subcutaneous , intraperitoneal and intravenous . Intramuscular administration is not recommended due to small muscle mass. Intracerebral administration

1026-608: Is required, and are usually referred to as stocks rather than strains . Over 400 standardized, inbred strains have been developed. Most laboratory mice are hybrids of different subspecies, most commonly of Mus musculus domesticus and Mus musculus musculus . Laboratory mice can have a variety of coat colours, including agouti, black and albino . Many (but not all) laboratory strains are inbred. The different strains are identified with specific letter-digit combinations; for example C57BL/6 and BALB/c . The first such inbred strains were produced in 1909 by Clarence Cook Little , who

1083-425: Is spontaneous. The duration of the estrous cycle is 4–5 days and lasts about 12 hours, occurring in the evening. Vaginal smears are useful in timed matings to determine the stage of the estrous cycle. Mating can be confirmed by the presence of a copulatory plug in the vagina up to 24 hours post-copulation. The presence of sperm on a vaginal smear is also a reliable indicator of mating. The average gestation period

1140-949: Is the Tg2576 strain of mice. The K670M and N671L double mutations seen in the human 695 splice-variant of the amyloid precursor protein (APP) are expressed by this strain. A hamster prion protein gene promoter , predominantly in neurons, drives the expression. When compared to non-transgenic littermates, Tg2576 mice show a five-fold rise in Aβ40 and a 10- to 15-fold increase in Aβ42/43. These mice develop senile plaques linked to cellular inflammatory responses because their brains have approximately five times as much transgenic mutant human APP than indigenous mouse APP. The mice exhibit main characteristics of Alzheimer's disease (AD), such as increased generation of amyloid fibrils with aging, plaque formation, and impaired hippocampus learning and memory. Tg2576 mice are

1197-493: Is unusually sensitive to pain and to cold, and analgesic medications are less effective in this strain. Unlike most laboratory mouse strains, the C57BL/6 drinks alcoholic beverages voluntarily. It is more susceptible than average to morphine addiction , atherosclerosis , and age-related hearing loss . When compared directly to BALB/c mice, C57BL/6 mice also express both a robust response to social rewards and empathy. BALB/c

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1254-663: The American Veterinary Medical Association issued new guidelines for CO 2 induction, stating that a flow rate of 10% to 30% volume/min is optimal for euthanasing laboratory mice. A recent study detected a murine astrovirus in laboratory mice held at more than half of the US and Japanese institutes investigated. Murine astrovirus was found in nine mice strains, including NSG , NOD-SCID , NSG-3GS , C57BL6 - Timp-3 , uPA-NOG , B6J , ICR, Bash2 , and BALB/C , with various degrees of prevalence. The pathogenicity of

1311-475: The microbiota , which directly affects the immune system and the development of pathological conditions. Moreover, persistent virus infections (for example, herpesviruses ) are activated in humans, but not in SPF mice with septic complications and may change the resistance to bacterial coinfections . "Dirty" mice are possibly better suitable for mimicking human pathologies. In addition, inbred mouse strains are used in

1368-537: The white-footed mouse ( Peromyscus leucopus ) and the North American deer mouse ( Peromyscus maniculatus ). Mice have been used in biomedical research since the 17th century when William Harvey used them for his studies on reproduction and blood circulation and Robert Hooke used them to investigate the biological consequences of an increase in air pressure. During the 18th century Joseph Priestley and Antoine Lavoisier both used mice to study respiration . In

1425-428: The 19th century Gregor Mendel carried out his early investigations of inheritance on mouse coat color but was asked by his superior to stop breeding in his cell "smelly creatures that, in addition, copulated and had sex". He then switched his investigations to peas but, as his observations were published in a somewhat obscure botanical journal, they were virtually ignored for over 35 years until they were rediscovered in

1482-646: The 20th and 21st Centuries. The Jackson Laboratory in Bar Harbor, Maine is currently one of the world's largest suppliers of laboratory mice, at around 3 million mice a year. The laboratory is also the world's source for more than 8,000 strains of genetically defined mice and is home of the Mouse Genome Informatics database. Breeding onset occurs at about 50 days of age in both females and males, although females may have their first estrus at 25–40 days. Mice are polyestrous and breed year round; ovulation

1539-499: The A246E FAD mutation. This crosses promotes the build-up of amyloid and plaque development in the CNS. This lends credence to the theory that AD pathogenesis is influenced by the interplay between APP and PS-1 gene products. Although Tg2576 mice do not perfectly replicate late-stage AD with cell death, they do offer a platform for researching the physiology and biochemistry of the illness.With

1596-451: The BALB/Lac substrain is much more docile. Most BALB/c mice substrains have a long reproductive life-span. There are noted differences between different BALB/c substrains, though these are thought to be due to mutation rather than genetic contamination. The BALB/cWt is unusual in that 3% of progeny display true hermaphroditism . A useful model for Alzheimer's disease (AD) in the lab

1653-603: The Care and Use of Laboratory Animals and the PHS policy. This accreditation is, however, not a prerequisite for federal funding, unlike the actual compliance. While mice are by far the most widely used animals in biomedical research, recent studies have highlighted their limitations. For example, the utility of rodents in testing for sepsis , burns , inflammation , stroke , ALS , Alzheimer's disease , diabetes , cancer , multiple sclerosis , Parkinson's disease , and other illnesses has been called into question by

1710-707: The U.K. are published each year. In the U.K. in 2013, there were a total of 3,077,115 regulated procedures undertaken on mice in scientific procedure establishments, licensed under the Act. In the U.S., laboratory mice are not regulated under the Animal Welfare Act administered by the USDA APHIS . However, the Public Health Service Act (PHS) as administered by the National Institutes of Health does offer

1767-459: The ability to accurately extrapolate findings to humans. Researchers have also noted that many studies involving mice are poorly designed, leading to questionable findings. Some studies suggests that inadequate published data in animal testing may result in irreproducible research, with missing details about how experiments are done are omitted from published papers or differences in testing that may introduce bias. Examples of hidden bias include

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1824-452: The associated high homology with humans, their ease of maintenance and handling, and their high reproduction rate, make mice particularly suitable models for human-oriented research. The laboratory mouse genome has been sequenced and many mouse genes have human homologues. Lab mice are sold at pet stores for snake food and can also be kept as pets . Other mouse species sometimes used in laboratory research include two American species,

1881-487: The chromogen) and oxydase (enzyme). John Cairns as recently as 2003 credited Lucien Cuénot with the one-gene one-enzyme hypothesis. The entry on " Albino " in the Encyclopædia Britannica (11th, 1911) does fully appreciate Cuénot's work on the relationship between determinants (genes) and ferments (enzymes): Before we can inquire into the cause and meaning of albinism it will be necessary first to consider

1938-547: The closest non- primate relatives of humans along with lagomorphs , treeshrews , and flying lemurs . Rodentia (rodents) Lagomorpha (rabbits, hares, pikas) Scandentia (treeshrews) Dermoptera (flying lemurs) Primates († Plesiadapiformes , Strepsirrhini , Haplorrhini ) Laboratory mice are the same species as the house mouse ; however, they are often very different in behaviour and physiology . There are hundreds of established inbred , outbred , and transgenic strains. A strain , in reference to rodents,

1995-413: The conclusion that three “mnemons” (genes) are responsible for the production of one “chromogen” or pigment and two “distases” enzymes . The pigment (if present) is acted upon by the enzymes to produce black or yellow colour. If no pigment is present the result is an albino mouse. Cuénot studied the offspring of various crosses between mice and concluded that these “mnemons” or genes were inherited in

2052-776: The design and execution of the tests themselves. In addition, the caging of laboratory animals may render them irrelevant models of human health because these animals lack day-to-day variations in experiences, agency, and challenges that they can overcome. The impoverished environments inside small mouse cages can have deleterious influences on biomedical results, especially with respect to studies of mental health and of systems that depend upon healthy psychological states. For example, researchers have found that many mice in laboratories are obese from excess food and minimal exercise, which alters their physiology and drug metabolism. Many laboratory animals, including mice, are chronically stressed, which can also negatively affect research outcomes and

2109-438: The dose of 100 mg per kg body weight) plus xylazine (in the dose of 5–10 mg per kg), injected by the intraperitoneal route. It has a duration of effect of about 30 minutes. Approved procedures for euthanasia of laboratory mice include compressed CO 2 gas, injectable barbiturate anesthetics , inhalable anesthetics, such as Halothane, and physical methods, such as cervical dislocation and decapitation. In 2013,

2166-486: The early 20th century. In 1902 Lucien Cuénot published the results of his experiments using mice which showed that Mendel's laws of inheritance were also valid for animals — results that were soon confirmed and extended to other species. In the early part of the 20th century, Harvard undergraduate Clarence Cook Little was conducting studies on mouse genetics in the laboratory of William Ernest Castle . Little and Castle collaborated closely with Abbie Lathrop who

2223-472: The female does not mate during the postpartum estrus, she resumes cycling 2–5 days post-weaning. Newborn males are distinguished from newborn females by noting the greater anogenital distance and larger genital papilla in the male. This is best accomplished by lifting the tails of littermates and comparing perinea . Mice are mammals of the clade (a group consisting of an ancestor and all its descendants) Euarchontoglires , which means they are amongst

2280-399: The head, snout, and shoulders, although barbering may appear anywhere on the body. Also self-barbering can occure. Both hair and vibrissae may be removed. Barbering is more frequently seen in female mice; male mice are more likely to display dominance through fighting. C57BL/6 has several unusual characteristics which make it useful for some research studies but inappropriate for others: It

2337-503: The help of transgenic mouse models, researchers can make progress in AD research by understanding the intricate relationships between gene products that are involved in the production of Aβ peptide.e physiology and biochemistry of the illness. Traditionally, laboratory mice have been picked up by the base of the tail. However, recent research has shown that this type of handling increases anxiety and aversive behaviour. Instead, handling mice using

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2394-472: The inheritance of white spotting in the mouse did not breed true. The mouse and population geneticist Sewall Wright credited Cuénot with the discovery of multiple alleles and the one-gene one-enzyme hypothesis. When writing Cuénot's obituary in 1951, Richard Goldschmidt credits Cuénot with the gene controlling enzyme hypothesis: In 1903 he [Cuénot] already understood the genic (genetic) control of pigment in terms of chromogen (genes were responsible for

2451-450: The inquiry being only in its initial stages, there is already good evidence to believe that Cuénot's theory is correct, and that an albino is an individual whose skin lacks the power to secrete either the ferment or the chromogen. It forms one but not both of these substances... Not only do albinos thus carry the determinants (genes) for pattern, but it has been known for some time that they also carry gametically, but never visible somatically,

2508-539: The knowledge as well. This is an indispensable tool for any researcher using the mouse as a model organism for their research, and for researchers interested in genes that share homology with the mouse genes. Various mouse research support resources including animal collections and free colony management software are also available at the MGI site. The Mouse Genome Database collects and curates comprehensive phenotype and functional annotations for mouse genes and alleles . This

2565-516: The man credited the "one gene one enzyme" hypothesis never recognized Cuénot's discovery that certain traits arose due to the presence or absence of an enzyme. Bateson did receive a letter from Charles Chamberlain Hurst in which he was urged to "read and digest the new Cuénot", work which explained some results in the field of mouse genetics, results which had been confusing for Bateson. Other scientists who were well known in Cuénot's own day and still into

2622-399: The many available strains includes - Since 1998, it has been possible to clone mice from cells derived from adult animals. There are many strains of mice used in research, however, inbred strains are usually the animals of choice for most fields. Inbred mice are defined as being the product of at least 20 generations of brother X sister mating, with all individuals being derived from

2679-559: The murine astrovirus was not known. In the U.K., as with all other vertebrates and some invertebrates, any scientific procedure which is likely to cause "pain, suffering, distress or lasting harm" is regulated by the Home Office under the Animals (Scientific Procedures) Act 1986 . U.K. regulations are considered amongst the most comprehensive and rigorous in the world. Detailed data on the use of laboratory mice (and other species) in research in

2736-448: The nature Of pigmentation... Subsequently (1903) L. Cuénot, in order to explain certain features in the hereditary transmission of coat colour in mice, postulated the hypothesis that the grey colour of the wild mouse (which is known to be a compound of black, chocolate and yellow pigments) may be due either to the interaction of a single ferment and three chromogens, or vice versa, to one chromogenic substance and three ferments... In spite of

2793-507: The overwhelming majority of studies, while the human population is heterogeneous, pointing to the importance of studies in interstrain hybrid, outbred , and nonlinear mice. An article in The Scientist notes, "The difficulties associated with using animal models for human disease result from the metabolic, anatomic, and cellular differences between humans and other creatures, but the problems go even deeper than that" including issues with

2850-409: The physical and behavioural characteristics of house mice; however, due to many generations of artificial selection, some of these characteristics now vary markedly. Due to the large number of strains of laboratory mice, it is impractical to comprehensively describe the appearance and behaviour of all of them; however, they are described below for two of the most commonly used strains. C57BL/6 mice have

2907-401: The present day, such as Clarence Little and Sewall Wright , and William E. Castle did credit Cuénot with pioneering work in genetics. For example, Clarence Little and William E. Castle did credit Cuénot with the discovery of the first lethal mutation. The mouse geneticist Clarence Little credited Cuénot with the idea and first evidence for multiple allelism , and recognizing that

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2964-408: The size of the human genome. Estimating the number of genes contained in the mouse genome is difficult, in part because the definition of a gene is still being debated and extended. The current count of primary coding genes in the laboratory mouse is 23,139. compared to an estimated 20,774 in humans. Various mutant strains of mice have been created by a number of methods. A small selection from

3021-640: The top 10 most popular strains according to Jackson Laboratories . The Jackson Labs DO ( Diversity Outbred ) project is a mouse breeding program using multiple inbred founder strains to create a genetically diverse population of mice for use in scientific research. These mice are designed for fine genetic mapping , and capture a large portion of the genetic diversity of the mouse genome. This project has resulted in over 1,000 genetically diverse mice which have been used to identify genetic factors for diseases such as obesity, cancer, diabetes, and alcohol use disorder. Laboratory mice have retained many of

3078-410: Was a French biologist. In the first half of the 20th century, Mendelism was not a popular subject among French biologists. Cuénot defied popular opinion and shirked the “pseudo-sciences” as he called them. Upon the rediscovery of Mendel's work by Correns , De Vries , and Tschermak , Cuénot proved that Mendelism applied to animals as well as plants. Cuénot spent two years working on mice and came to

3135-492: Was a breeder of fancy mice and rats which she marketed to rodent hobbyists and keepers of exotic pets, and later began selling in large numbers to scientific researchers. Together they generated the DBA (Dilute, Brown and non-Agouti) inbred mouse strain and initiated the systematic generation of inbred strains. The mouse has since been used extensively as a model organism and is associated with many important biological discoveries of

3192-573: Was called the "Encyclopedia of the Mouse Genome" and distributed via floppy disk semi-annually to around 300 scientists around the world. In 1992, that group joined with the team responsible for developing the "Genomic Database for Mouse", led by Muriel T. Davisson and Thomas H. Roderick, to start the "Mouse Genome Informatics" project. That project resulted in the first online release of the "Mouse Genome Database" in 1994. Laboratory mouse#Laboratory mice The laboratory mouse or lab mouse

3249-512: Was influential in promoting the mouse as a laboratory organism. In 2011, an estimated 83% of laboratory rodents supplied in the U.S. were C57BL/6 laboratory mice. Sequencing of the laboratory mouse genome was completed in late 2002 using the C57BL/6 strain. This was only the second mammalian genome to be sequenced after humans. The haploid genome is about three billion base pairs long (3,000 Mb distributed over 19 autosomal chromosomes plus 1 respectively 2 sex chromosomes), therefore equal to

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