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Mice are the most commonly used mammalian research animal model with hundreds of established inbred, outbred, and transgenic strains. They are common experimental animals in biology and psychology, primarily because they are mammals, are relatively easy to maintain and handle, reproduce quickly, and share a high degree of homology with humans. The mouse genome has been sequenced, and many mouse genes have human homologues. In addition to being small, relatively inexpensive, and easily maintained, several generations of mice can be observed in a relatively short period of time as mice reproduce very quickly.
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, so as to make them genetically almost identical. The different strains are identified with specific letter-digit combinations; for example C57BL/6 and BALB/c. The first such inbred strains were produced by Clarence Cook Little in 1909. Little was influential in promoting the mouse as a laboratory organism.
Legislation of use in scienceEdit
In the UK, as with all other vertebrates and some invertebrates, any scientific procedure which is likely to cause lasting distress or suffering is regulated by the Home Office under the Animals (Scientific Procedures) Act 1986. Detailed data on the use of mice and other species in research in the UK are published each year. In the UK in 2012, there was a total of 3,058,800 regulated procedures on mice in research, which represents 74% of all scientific procedures on animals in the UK in that year.
In the United States, 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 a standard for their care and use. Compliance with PHS is required to receive federal funding. PHS policy is administered by the Office of Laboratory Animal Welfare. Many academic research institutes seek accreditation voluntarily, often through Association for Assessment and Accreditation of Laboratory Animal Care, which maintains the standards of care found within The Guide for the Care and Use of Laboratory Animals and the PHS policy. This accreditation is voluntary, not a prerequisite, for federal funding.
Sequencing of the mouse genome was completed in late 2002. The haploid genome is about three billion base pairs long (3000 Mb distributed over 20 chromosomes), therefore equal to the size of the human genome.[dead link]
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 is 23,139. For comparison, humans have an estimated 20,774.
The t-haplotype is a selfish element that works to disable the function of the wild house mouse, Mus musculus, sperm to ensure the fertilization of the female egg with their own sperm. This gamete killer designed and structured to suppress recombination of genes, is a single unit, of linked genes, located near the centromere of chromosome 17 and is approximately 30-40 Mb long. One part of the t-haplotype is the responder-insensitive allele Tcr. Tcr gives protection from the distorting drivers, since it shows haploid-specific expression, which means only sperm that carry the haploid are rescued from being killed. While advantageous, the frequency of this selfish element is reported as low.
The low t–haplotype frequency in the wild house mouse population is a paradox. Although +/t male mice carry equal ratios of both gamete types (+ and t) and the wild type chromosome becomes functionally inactivated as well as 90% of the offspring inherit the t chromosomes, wild house mouse populations have remained polymorphic. It would be hypothesized that the high transmission distortion ratio of t-haplotypes would become fixed in a natural population, if 90% of the offspring were inheriting the t chromosome, but due to several factors, this is not the case. Investigations of different subspecies mice populations in different locations have found there were low t frequencies in enclosure populations, as well as in different subspecies. Huang et al. (2001), in Taiwan, observed a low frequency in the subspecies, Mus castaneus, which has also been observed by both Ardlie and Silver (1998) and Carroll et al. (2004). Based on these findings, the general mechanisms of these low t frequencies in mouse populations are similar across subspecies and geographical location, making the unraveling of this paradox beneficial to not only the Mus domesticus species of mouse, but also for other species of mouse, such as Mus castaneus.
Explanations for the low frequency of t-haplotypes include factors such as population size, inbreeding, heterozygosity, and polyandry in the wild house mouse population.
Mutant and transgenic strains Edit
Various mutant strains of mice have been created by a number of methods. A small selection from the many available strains:
- Mice resulting from ordinary breeding
- NOD mice, which develop diabetes mellitus type 1.
- MRL mice with unusual regenerative capacities
- "Waltzing" mice, which walk in a circular pattern due to a mutation adversely affecting their inner ears
- Immunodeficient nude mice, lacking hair and a thymus: The mice do not produce T lymphocytes, therefore do not mount cellular immune responses. They are used for research in immunology and transplantation.
- Severe combined immunodeficient, with an almost completely defective immune system
- Transgenic mice, with foreign genes inserted into their genome
- Knockout mice, where a specific gene was made inoperable by a technique known as gene knockout: The purpose is to study the function of the gene's product or to simulate a human disease.
Since 1998, it has been possible to clone mice from cells derived from adult animals.
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 is also possible. Each procedure has recommended injection site, approximate needle gauge and recommended maximal injected volume at a single time at one site, as given in table:
|Route||Recommended site||Needle gauge||Maximal volume|
|subcutaneous||dorsum, between scapula||25-26 ga||2-3 ml|
|intraperitoneal||left lower quadrant||25-27 ga||2-3 ml|
|intravenous||lateral tail vein||27-28 ga||0.2 ml|
|intramuscular||hindlimb, caudal thigh||26-27 ga||0.05 ml|
A common regimen for general anesthesia for the house mouse is ketamine (in 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 CO2 gas, injectable barbiturate anesthetics, inhalable anesthetics, such as Halothane, and physical methods, such as cervical dislocation and decapitation.
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 degree of prevalence. The pathogenicity of the murine astrovirus was not known.
- ↑ MGI — Biology of the Laboratory Mouse. Informatics.jax.org. URL accessed on 2010-07-29.
- ↑ Crow JF (August 2002). C. C. Little, cancer and inbred mice. Genetics 161 (4): 1357–61.
- ↑ (2013). Annual Statistics of Scientific Procedures on Living Animals: Great Britain 2012. Home Office (UK). URL accessed on July 30, 2013.
- ↑ Office of Laboratory Animal Welfare: PHS Policy on Humane Care and Use of Laboratory Animals. Grants.nih.gov. URL accessed on 2010-07-29.
- ↑ No items found - Books Results
- ↑ Mouse assembly and gene annotation. Ensembl. URL accessed on 29 July 2013.
- ↑ Human assembly and gene annotation. Ensembl. URL accessed on 29 July 2013.
- ↑ Silver L (1993). The peculiar journey of a selfish chromosome: mouse t-haplotypes and meiotic drive. Trends in Genetics 9.
- ↑ Lyon, M. 2003. Transmission ratio distortion in mice. Annual Review Genetics 37:393-408.
- ↑ 10.0 10.1 10.2 Ardlie K., Silver L. (1998). Low frequency of t haplotypes in natural populations of house mice (Mus musculus domesticus). Evolution 52: 1185–1196.
- ↑ Huang , Ardlie K.G., Yu H.-T. (2001). Frequency and distribution of t-haplotypes in the southeast asian house mouse (Mus musculus castaneus) in Taiwan. Molecular Ecology 10: 2349–2354.
- ↑ Carroll L., Meagher S., Morrison L., Penn D., Potts W. (2004). Fitness effects of a selfish gene (the Mus t complex) are revealed in an ecological context. Evolution 58: 1318–1328.
- ↑ JAX Mice Database — 002983 MRL.CBAJms-Fas/J. Jaxmice.jax.org. URL accessed on 2010-07-29.
- ↑ 14.0 14.1 14.2 14.3 Guidelines for Selecting Route and Needle Size. Duke University and Medical Center - Animal Care & Use Program. URL accessed on April 2011.
- ↑ A Compendium of Drugs Used for Laboratory Animal Anesthesia, Analgesia, Tranquilization and Restraint at Drexel University College of Medicine. Retrieved April 2011
- ↑ 16.0 16.1 Guidelines for Systemic Anesthetics (Mouse) From Duke University and Medical Center - Animal Care & Use Program. Retrieved April 2011
- ↑ Euthanasia. Basic Biomethodology for Laboratory Mice. URL accessed on 2012-10-17.
- ↑ Ng TFF, Kondov NO, Hayashimoto N, Uchida R, Cha Y, et al. (2013) "Identification of an Astrovirus Commonly Infecting Laboratory Mice in the US and Japan". PLoS ONE 8(6): e66937. doi:10.1371/journal.pone.0066937