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Laboratory mouse

 

Laboratory mouse

An albino SCID laboratory mouse
A laboratory mouse with intermediate coat colour

The laboratory mouse is a small mammal of the order rodentia which is bred and kept for scientific research. 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, psychology, medicine and other scientific disciplines. Mice belong to the Euarchontoglires clade, which includes humans. This close relationship, 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.[1]

Other mouse species sometimes used in laboratory research include the American white-footed mouse (Peromyscus leucopus) and the deer mouse (Peromyscus maniculatus).

Contents

  • History as a biological model 1
  • Reproduction 2
  • Genetics and strains 3
    • Genome 3.1
    • Mutant and transgenic strains 3.2
  • Appearance and behaviour 4
    • C57BL/6 4.1
    • BALB/c 4.2
  • Husbandry 5
    • Nutrition 5.1
    • Injection procedures 5.2
    • Anaesthesia 5.3
    • Euthanasia 5.4
  • Pathogen susceptibility 6
  • Legislation in research 7
    • United Kingdom 7.1
    • United States 7.2
  • See also 8
  • References 9
  • Further reading 10
  • External links 11

History as a biological model

Mice have been used in biomedical research since the 16th 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.[2] During the 18th Century Joseph Priestley and Antoine Lavoisier both used mice to study respiration. In 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".[2] 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 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.[2]

In the early part of the 20th century

  • Biology of the Mouse, from the Louisiana Veterinary Medical Association
  • Nature Mouse Special 2002
  • Biology of Laboratory Rodents by David G. Besselsen

Further reading

  • Mus musculusPictures, movies and applets showing the anatomy of , from www.digimorph.org
  • Michael Purdy: "Researchers add mice to list of creatures that sing in the presence of mates"-Study of male mouse "song" with mouse song recording (MP3), by Washington University Medical School
  • Arkive Photographs.Short text.
  • Mus musculusHigh-Resolution Brain Maps and Brain Atlases of

Media

Genetics

Taxonomy

External links

  • Musser, G.G.; Carleton, M.D. (2005). "Superfamily Muroidea". In Wilson, D.E.; Reeder, D.M. Mammal Species of the World: a taxonomic and geographic reference (3rd ed.). Baltimore: Johns Hopkins University Press. pp. 894–1531.  
  • Nyby J. (2001). "Ch. 1 Auditory communication in adults". In Willott, James F. Handbook of Mouse Auditory Research: From Behavior to Molecular Biology. Boca Raton: CRC Press. pp. 3–18. 

Further reading

  1. ^ "MGI — Biology of the Laboratory Mouse". Informatics.jax.org. Retrieved 2010-07-29. 
  2. ^ a b c d Hedrich, Hans (ed.). "The house mouse as a laboratory model: a historical perspective". The Laboratory Mouse. Elsevier Science.  
  3. ^ Steensma, David P.; Kyle Robert A., Shampo Marc A. (November 2010). "Abbie Lathrop, the "Mouse Woman of Granby": Rodent Fancier and Accidental Genetics Pioneer". Mayo Clinic Proceedings (Mayo Foundation for Medical Education and Research) 85 (11): e83.  
  4. ^ Pillai, Shiv. "History of Immunology at Harvard". Harvard Medical School:About us. Harvard Medical School. Retrieved 19 December 2013. 
  5. ^ a b c d Louisiana Veterinary Medical Association
  6. ^ "Rules and guidelines for nomenclature of mouse and rat strains". 
  7. ^ "Outbred stocks". 
  8. ^ Crow JF (August 2002). "C. C. Little, cancer and inbred mice". Genetics 161 (4): 1357–61.  
  9. ^ a b c Engber, D. (2011). "The trouble with Black-6". Retrieved November 19, 2013. 
  10. ^ "Mouse assembly and gene annotation".  
  11. ^ "Human assembly and gene annotation".  
  12. ^ "JAX Mice Database — 002983 MRL.CBAJms-Fas/J". Jaxmice.jax.org. Retrieved 2010-07-29. 
  13. ^ Connor, A..B. (2006). "Aurora’s Guide to Mo use Colony Management". Cell Migration Gateway. CMC Activity Center. Retrieved 19 December 2013. 
  14. ^ Garner, J.P., Weisker, S.M., Dufour, B. and Mench, J.A., (2004). Barbering (fur and whisker trimming) by laboratory mice as a model of human trichotillomania and obsessive-compulsive spectrum disorders. Comparative Medicine, 54: 216-24 [1]
  15. ^ Sarna JR, Dyck RH, Whishaw IQ (February 2000). "The Dalila effect: C57BL6 mice barber whiskers by plucking".  
  16. ^ Mogil JS, Wilson SG, Bon K, et al. (March 1999). "Heritability of nociception I: responses of 11 inbred mouse strains on 12 measures of nociception". Pain 80 (1-2): 67–82.  
  17. ^ a b "BALB/c". Inbred Strains of Mice. Jackson Laboratory. Retrieved 2007-04-16. 
  18. ^ "BALB/cByJ". Jax Mice Data Sheet. Jackson Laboratory. Retrieved 2007-04-16. 
  19. ^ "BALB/cJ". Jax Mice Data Sheet. Jackson Laboratory. Archived from the original on 11 April 2007. Retrieved 2007-04-16. 
  20. ^ Southwick C. H. and Clark L. H. (1966) Aggressive behaviour and exploratory activity in fourteen mouse strains. Am. Zool. 6, 559.
  21. ^ Hilgers J., van Nie R., Ivanyi D., Hilkens J., Michalides R., de Moes J., Poort-Keesom R., Kroezen V., von Deimling O., Kominami R., and Holmes R. (1 985) Genetic differences in BALB/c sublines. Curr. Top. Microbiol. Immunol. 122, 19-30.
  22. ^ Eicher E. M., Beamer W. G., Washburn L. L., and Whitten W. K. (1980) A cytogenetic investigation of inherited true hermaphroditism in BALB/cWt mice. Cytogenet. Cell Genet. 28, 104-115.
  23. ^ Mouse: Northwestern University Ecodome Information Page
  24. ^ a b c d "Guidelines for Selecting Route and Needle Size". Duke University and Medical Center - Animal Care & Use Program. Archived from the original on 17 Jan 2005. Retrieved April 2011. 
  25. ^ A Compendium of Drugs Used for Laboratory Animal Anesthesia, Analgesia, Tranquilization and Restraint at Drexel University College of Medicine. Retrieved April 2011
  26. ^ a b Guidelines for Systemic Anesthetics (Mouse) From Duke University and Medical Center - Animal Care & Use Program. Retrieved April 2011
  27. ^ "Euthanasia". Basic Biomethodology for Laboratory Mice. Retrieved 2012-10-17. 
  28. ^ 2013 AVMA Guidelines for the Euthanasia of Animals
  29. ^ 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. article doi:10.1371/journal.pone.0066937
  30. ^ Anon. "Animal Research". Policy issues. Society of Biology. Retrieved 18 October 2014. 
  31. ^ "Annual Statistics of Scientific Procedures on Living Animals: Great Britain 2012". Home Office (UK). 2013. Retrieved July 30, 2013. 
  32. ^ Anon (2014). "Annual Statistics of Scientific Procedures on Living Animals Great Britain 2013". National statistics. Home Office. p. 26. Retrieved 18 October 2014. 
  33. ^ "Office of Laboratory Animal Welfare: PHS Policy on Humane Care and Use of Laboratory Animals". Grants.nih.gov. Retrieved 2010-07-29. 

References

See also

In the US, 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 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 the Care and Use of Laboratory Animals and the PHS policy. This accreditation is voluntary, not a prerequisite, for federal funding.[33]

United States

In the UK, 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. UK regulations are considered amongst the most comprehensive and rigorous in the world.[30] Detailed data on the use of laboratory mice (and other species) in research in the UK are published each year.[31] In the UK in 2013, there were a total of 3,077,115 regulated procedures on mice in scientific procedure establishments, licensed under the Act.[32]

United Kingdom

Legislation in research

A recent study detected a murine astrovirus in laboratory mice held at more than half of the US and Japanese institutes investigated.[29] 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 the murine astrovirus was not known.

Pathogen susceptibility

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.[27] In 2013, 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.[28]

Euthanasia

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.[26] It has a duration of effect of about 30 minutes.[26]

Anaesthesia

To facilitate intravenous injection into the tail, laboratory mice can be carefully warmed under heat lamps to vasodilate the vessels.[24]

Route Recommended site[24] Needle gauge[24] Maximal volume[25]
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
intracerebral cranium 27 ga
and recommended maximum injected volume at a single time at one site, as given in the table below: needle gauge is also possible. Each route has a recommended injection site, approximate Intracerebral administration [24] is not recommended due to small muscle mass.Intramuscular administration. intravenous and intraperitoneal, subcutaneous of injections in laboratory mice are mainly Routes of administration

Injection procedures

In nature, mice are usually herbivores, consuming a wide range of fruit or grain.[23] 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 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.[5]

Nutrition

Laboratory mouse (note the ear tag)

Husbandry

There are noted differences between different BALB/c substrains, though these are thought to be due to mutation rather than genetic contamination.[21] The BALB/cWt is unusual in that 3% of progeny display true hermaphroditism.[22]

Male BALB/c mice are aggressive and will fight other males if housed together. However, the BALB/Lac substrain is much more docile.[20] Most BALB/c mice substrains have a long reproductive life-span.[17]

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.[18][19]

BALB/c 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.[17]

BALB/c laboratory mice

BALB/c

C57BL/6 has several unusual characteristics which make it useful for some research studies but inappropriate for others: It is unusually sensitive to pain and to cold, and analgesic medications are less effective in this strain.[16] 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.[9]

Group-housed C57BL/6 mice (and other strains) display barbering behaviour, in which the dominant mouse in a cage selectively removes hair from its subordinate cage mates.[14] Mice that have been barbered extensively can have large bald patches on their bodies, commonly around the head, snout, and shoulders, although barbering may appear anywhere on the body. 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.[15]

C57BL/6 mice have 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.[13]

A female C57BL/6 laboratory mouse

C57BL/6

Laboratory mice have retained many of 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 these, however, they are described below for two of the most commonly used strains.

Appearance and behaviour

Since 1998, it has been possible to clone mice from cells derived from adult animals.

Various mutant strains of mice have been created by a number of methods. A small selection from the many available strains includes -

Comparison of a knockout Obese mouse (left) and a normal laboratory mouse (right).
Two mice expressing enhanced green fluorescent protein under UV-illumination flanking one plain mouse from the non-transgenic parental line.

Mutant and transgenic strains

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.[9] The haploid genome is about three billion base pairs long (3,000 Mb distributed over 20 chromosomes), therefore equal to 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.[10] compared to an estimated 20,774 in humans.[11]

Genome

[9] In 2011, an estimated 83% of laboratory rodents supplied in the U.S. were C57BL/6 laboratory mice.[8]. Laboratory mice can have a variety of coat colours, including agouti, black and Mus musculus musculus and Mus musculus domesticus Most laboratory mice are hybrids of different subspecies, most commonly of

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, 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 is required, and are usually referred to as stocks rather than strains.[6][7] Over 400 standard, inbred strains have been developed.

Euarchontoglires
Glires

Rodentia (rodents)


Lagomorpha (rabbits, hares, pikas)


Euarchonta

Scandentia (treeshrews)

Primatomorpha

Dermoptera (flying lemurs)



Primates (†Plesiadapiformes, Strepsirrhini, Haplorrhini)





. primates and other flying lemurs, treeshrews, lagomorphs ( a group consisting of an ancestor and all its descendants), which means they are amongst the closest relatives of humans along with cladeMice are mammals of the Glires

Genetics and strains

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 perineums.[5]

The average gestation period 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 the female does not mate during the postpartum estrus, she resumes cycling 2–5 days post-weaning.[5]

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 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.[5]

1 day old pups

Reproduction

[2]

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