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{{Short description|Mouse used for scientific research}} [[File:Vector diagram of laboratory mouse (black and white).svg|250px|alt=Line drawing of a laboratory mouse|thumb|The [[Albinism in biology|albino]] laboratory mouse is an iconic model organism for scientific research in a variety of fields]] [[File:Scid mouse.jpg|thumb|250px|An [[Severe combined immunodeficiency (non-human)|SCID]]|alt=Albino [[Severe combined immunodeficiency (non-human)|SCID]]]] [[File:Lab mouse mg 3244.jpg|thumb|250px|Intermediate coat colour|alt=With intermediate coat colour]] [[File:Pet lab mouse in the grass.jpg|thumb|Kept as a pet|alt=Kept as a pet standing on a patch of grass]] The '''laboratory mouse''' or '''lab mouse''' is a small [[mammal]] of the order [[Rodent]]ia which is bred and used for [[scientific research]] or [[live food|feeders]] for certain pets. [[Mice]] used in [[laboratories]] are usually of the species ''[[House mouse|Mus musculus]]''. They are the most commonly used mammalian [[model organism|research model]] and are used for research in [[genetics]], [[physiology]], [[psychology]], [[medicine]] and other [[scientific discipline]]s. Mice belong to the [[Euarchontoglires]] clade, which includes [[human]]s. This close relationship, the associated high [[homology (biology)|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.<ref>{{cite web|url=http://www.informatics.jax.org/greenbook/frames/frame11.shtml |title=MGI — Biology of the Laboratory Mouse |publisher=Informatics.jax.org |access-date=29 July 2010}}</ref> Lab mice are sold at [[pet store]]s for [[snake]] [[food]] and can also be kept as [[pet]]s. Other mouse species sometimes used in laboratory research include two American species, the [[white-footed mouse]] (''Peromyscus leucopus'') and the eastern deer mouse (''[[Peromyscus maniculatus]]''). == History as a biological model == 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.<ref name="Hedrich">{{cite book|title=The Laboratory Mouse|editor= Hedrich, Hans |publisher=Elsevier Science|chapter=The house mouse as a laboratory model: a historical perspective|isbn=9780080542539|date= 2004-08-21 }}</ref> During the 18th century [[Joseph Priestley]] and [[Antoine Lavoisier]] both used mice to study [[Respiratory system|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".<ref name="Hedrich"/> 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.<ref name="Hedrich"/> In the early part of the 20th century, [[Harvard University|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 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.<ref name="Steensma">{{cite journal | vauthors = Steensma DP, Kyle RA, Shampo MA | title = Abbie Lathrop, the "mouse woman of Granby": rodent fancier and accidental genetics pioneer | journal = Mayo Clinic Proceedings | volume = 85 | issue = 11 | pages = e83 | date = November 2010 | pmid = 21061734 | pmc = 2966381 | doi = 10.4065/mcp.2010.0647 }}</ref> Together they generated the DBA (Dilute, Brown and non-Agouti) inbred mouse strain and initiated the systematic generation of inbred strains.<ref>{{cite web |url=https://immunology.hms.harvard.edu/about-us/history |title=History of Immunology at Harvard |vauthors=Pillai S |work=Immunology.HMS.Harvard.edu |publisher=Harvard Medical School |access-date=19 December 2013 |archive-date=20 December 2013 |archive-url=https://web.archive.org/web/20131220022416/https://immunology.hms.harvard.edu/about-us/history |url-status=dead }}</ref> The mouse has since been used extensively as a [[model organism]] and is associated with many important biological discoveries of the 20th and 21st centuries.<ref name="Hedrich"/> 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.<ref name="economist.com">{{Cite news |url= https://www.economist.com/news/christmas-specials/21712058-evolution-scientific-mainstay-worlds-favourite-lab-animal-has-been-found |title=The world's favourite lab animal has been found wanting, but there are new twists in the mouse's tale |newspaper=The Economist |access-date=10 January 2017}}</ref> 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.<ref>{{Cite web |url=https://www.criver.com/files/pdfs/rms/jax/rm_d_jax_eu_partnership.aspx |title=JAX Mice and Research Services |date=2016 |work=CRiver.com |publisher=Charles River Laboratories |access-date=10 January 2016 |archive-url=https://web.archive.org/web/20150818061606/http://www.criver.com/files/pdfs/rms/jax/rm_d_jax_eu_partnership.aspx |archive-date=18 August 2015 |url-status=dead }}</ref> == Reproduction == [[File:Day-old mice.JPG|right|thumb|1-day-old pups]] 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.<ref name=lvma /> 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 (animal)|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 (biology)|hybrid]] mice. The young are called pups and weigh {{convert|0.5|-|1.5|g|abbr=on}} at birth, are hairless, and have closed eyelids and ears. Pups are weaned at 3 weeks of age when they weigh about {{convert|10|-|12|g|abbr=on}}. If the female does not mate during the postpartum estrus, she resumes cycling 2–5 days post-weaning.<ref name=lvma/> 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 [[littermate]]s and comparing [[perineum|perinea]].<ref name=lvma/> ==Genetics and strains== Mice are mammals of the [[clade]] (a group consisting of an ancestor and all its descendants) [[Euarchontoglires]], which means they are amongst the closest non-[[primate]] relatives of humans along with [[Lagomorpha|lagomorphs]], [[treeshrew]]s, and [[flying lemurs]]. {{Clade | label1=[[Euarchontoglires]] | 1={{Clade | label1='''Glires''' | 1={{Clade | 1=[[Rodent]]ia (rodents) | 2=[[Lagomorpha]] (rabbits, hares, pikas)}} | label2=[[Euarchonta]] | 2={{Clade | 1=[[Treeshrew|Scandentia]] (treeshrews) | label2=[[Primatomorpha]] | 2={{Clade | 1=[[Colugo|Dermoptera]] (flying lemurs) | 2={{Clade | 1=[[Primate]]s (†[[Plesiadapiformes]], [[Strepsirrhini]], [[Haplorrhini]])}} }} }} }} }} Laboratory mice are the same species as the [[house mouse]]; however, they are often very different in [[Ethology|behaviour]] and [[physiology]]. There are hundreds of established [[inbred]], [[outbred]], and [[transgenic]] strains. A ''[[strain (biology)|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 [[genotype]]s are unnecessary or a population with genetic variation is required, and are usually referred to as ''stocks'' rather than ''strains''.<ref name=mgi>{{Cite web|url=http://www.informatics.jax.org/mgihome/nomen/strains.shtml#oacc|title=MGI-Guidelines for Nomenclature of Mouse and Rat Strains|website=www.informatics.jax.org}}</ref><ref name="isogenic">{{cite web |title=Outbred stocks |date= 15 February 2019|url= http://isogenic.info/html/outbred_stocks.html}}</ref> Over 400 standardized, inbred strains have been developed.{{citation needed|date=December 2018}} 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 [[C. C. Little|Clarence Cook Little]], who was influential in promoting the mouse as a laboratory organism.<ref>{{cite journal | vauthors = Crow JF | title = C. C. Little, cancer and inbred mice | journal = Genetics | volume = 161 | issue = 4 | pages = 1357–61 | date = August 2002 | doi = 10.1093/genetics/161.4.1357 | pmid = 12196385 | pmc = 1462216 | url = http://www.genetics.org/cgi/content/full/161/4/1357 }}</ref> In 2011, an estimated 83% of laboratory rodents supplied in the U.S. were C57BL/6 laboratory mice.<ref name="Trouble">{{cite journal |url= http://www.slate.com/articles/health_and_science/the_mouse_trap/2011/11/black_6_lab_mice_and_the_history_of_biomedical_research.html |title=The trouble with Black-6 |journal=Slate | vauthors = Engber D |date=2011 |access-date=19 November 2013}}</ref> === Genome === 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.<ref name="Trouble" /> The [[haploid]] genome is about three billion [[base pair]]s long (3,000 Mb distributed over 19 autosomal chromosomes plus 1 respectively 2 sex chromosomes), therefore equal to the size of the human genome.{{citation needed|date=August 2021}} 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.<ref name="Ensembl">{{cite web |title=Mouse assembly and gene annotation |url= http://useast.ensembl.org/Mus_musculus/Info/Annotation |work=[[Ensembl]] |access-date=29 July 2013}}</ref> compared to an estimated 20,774 in humans.<ref name="Ensembl" /> === Mutant and transgenic strains === [[File:GFP Mice 01.jpg|right|thumb|170px|Two mice expressing enhanced green fluorescent protein under UV-illumination flanking one plain mouse from the non-transgenic parental line]] [[File:Fatmouse.jpg|thumb|170px|Comparison of a knockout [[ob/ob mouse|obese mouse]] (left) and a normal laboratory mouse (right)]] Various [[mutant]] strains of mice have been created by a number of methods. A small selection from the many available strains includes - * Mice resulting from ordinary [[Reproduction|breeding]] and [[inbreeding]]: ** [[NOD mice|Non-obese diabetic (NOD) mice]], which develop [[diabetes mellitus type 1]]. ** [[Murphy Roths large]] (MRL) mice, with unusual [[Regeneration (biology)|regenerative]] capacities<ref>{{cite web|url=http://jaxmice.jax.org/strain/002983.html |title=JAX Mice Database — 002983 MRL.CBAJms-Fas/J |work=Jaxmice.jax.org |publisher=[[Jackson Laboratory]] |location=Bar Harbor, Maine |access-date=29 July 2010}}</ref> ** [[Japanese waltzing mice]], which walk in a circular pattern due to a mutation adversely affecting their inner [[ear]]s ** [[Immunodeficient]] [[Nude mouse|nude mice]], lacking hair and a [[thymus]]: these mice do not produce [[T lymphocyte]]s; therefore, they do not mount cellular immune responses. They are used for research in [[immunology]] and [[Organ transplant|transplantation]]. ** [[Severe combined immunodeficiency]] (SCID) mice, with an almost completely defective [[immune system]] ** [[FVB mice]], whose large litter sizes and large oocyte pronuclei expedite use in genetic research ** {{visible anchor|Toxic milk mouse|text=[[Toxic milk mouse|Toxic milk mice]]}}, which fail to recruit nutrient copper into milk causing pup death. It is caused by an [[autosomal]] [[recessive (genetics)|recessive]] mutation ''[[tx (gene)|tx]]'' which arose in an inbred. Theophilos et al. 1996 found this to be genetic and localized to chromosome 8, near the [[centromere]].<ref name="Pierson-et-al-2019">{{cite journal | last1=Pierson | first1=Hannah | last2=Yang | first2=Haojun | last3=Lutsenko | first3=Svetlana | title=Copper Transport and Disease: What Can We Learn from Organoids? | journal=[[Annual Review of Nutrition]] | publisher=[[Annual Reviews (publisher)|Annual Reviews]] | volume=39 | issue=1 | date=2019-08-21 | issn=0199-9885 | doi=10.1146/annurev-nutr-082018-124242| pmc=7065453 | pages=75–94| pmid=31150593 }}</ref> * [[Genetically modified mouse|Transgenic mice]], with foreign genes inserted into their genome: ** Abnormally large mice, with an inserted rat [[growth hormone]] gene ** [[Oncomouse|Oncomice]], with an activated [[oncogene]], so as to significantly increase the incidence of [[cancer]] ** [[Long-term potentiation#Spatial memory|Doogie mice]], with enhanced [[NMDA receptor]] function, resulting in improved memory and learning * [[Knockout mouse|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 ** Obese mice, prone to obesity due to a carboxypeptidase E deficiency ** Strong muscular mice, with a disabled [[myostatin]] gene, nicknamed "mighty mice". Since 1998, it has been possible to [[Cloning|clone]] mice from cells derived from adult animals. ===Commonly used inbred strains=== There are many [[Strain (biology)|strains]] of [[laboratory mice|mice]] used in research, however, [[Inbreeding|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 a single breeding pair.<ref>{{cite web | url=https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/inbred-strain | title=Inbred Strain - an overview | ScienceDirect Topics }}</ref> Inbred mice have several traits that make them ideal for research purposes. They are [[Isogenic line|isogenic]], meaning that all animals are nearly genetically identical.<ref name="auto4">{{cite book | chapter-url=https://doi.org/10.1016/B978-0-12-374984-0.00781-6 | doi=10.1016/B978-0-12-374984-0.00781-6 | chapter=Inbred Strain | title=Brenner's Encyclopedia of Genetics | year=2001 | last1=Silver | first1=L. | page=53 | isbn=9780080961569 }}</ref> Approximately 98.7% of the [[genetic loci]] in the [[genome]] are [[homozygous]], so there are probably no "hidden" [[recessive trait]]s that could cause problems.<ref name="auto4"/> They also have very unified [[phenotype]]s due to this stability.<ref name="auto4"/> Many inbred strains have well documented traits that make them ideal for specific types of research. The following table shows the top 10 most popular strains according to [[Jackson Laboratory|Jackson Laboratories]].<br> {| class="wikitable sortable" |+ Common inbred strains of laboratory mice available from Jackson Laboratories |- ! Strain !! Coat color<ref name="auto2">{{cite web |url=https://jackson.jax.org/rs/444-BUH-304/images/Poster_Mouse_Coat_Color.pdf |title=Poster Mouse Coat Color|website=jax.org|access-date=4 June 2023}}</ref> !! Common research uses !! Total Pubmed publications referencing the strain as of April 19, 2023<ref>{{Cite web|url=https://pubmed.ncbi.nlm.nih.gov/|title=PubMed|website=PubMed}}</ref> |- | C3HeB/FeJ || Agouti || [[Immunology]], [[inflammation]], [[autoimmunity]]<ref>{{cite web | url=https://www.jax.org/strain/000658 | title=000658 - C3HFe Strain Details }}</ref> || 482 |- | NOD/ShiLtJ || Albino || Autoimmune [[type 1 diabetes]]<ref name="auto">{{cite web | url=https://www.jax.org/strain/001976 | title=001976 - NOD Strain Details }}</ref> || 105 |- | DBA/1J || Dilute brown || [[Rheumatoid arthritis]]<ref>{{cite web | url=https://www.jax.org/strain/000670 | title=000670 - DBA1 Strain Details }}</ref> || 445 |- | [[BALB/c|BALB/cByJ]] || Albino || [[Cancer]], [[Cardiovascular disease|cardiovascular]], [[immunology]]<ref>{{cite web | url=https://www.jax.org/strain/001026 | title=001026 - Strain Details }}</ref> || 628 |- | DBA/2J || Dilute brown || [[Cardiovascular disease|Cardiovascular]], [[dermatology]], [[developmental biology]]<ref>{{cite web | url=https://www.jax.org/strain/000671 | title=000671 - DBA2 Strain Details }}</ref> || 2,722 |- | C3H/HeJ || Agouti || [[Cancer]], [[Cardiovascular disease|cardiovascular]], [[hematology]]<ref>{{cite web | url=https://www.jax.org/strain/000659 | title=000659 - C3H Strain Details }}</ref> || 4,037 |- | [[C57BL/6|C57BL/6J]] || Black || General purpose, background<ref name="auto1">{{cite web | url=https://www.jax.org/strain/000664 | title=000664 - B6 Strain Details }}</ref> || 25,723 |- | SJL/J || Albino || [[Cancer]], [[Cardiovascular disease|cardiovascular]], [[dermatology]]<ref>{{cite web | url=https://www.jax.org/strain/000686 | title=000686 - SJL Strain Details }}</ref> || 1,448 |- | FVB/NJ || Albino || [[Immunology]], [[inflammation]], [[autoimmunity]]<ref>{{cite web | url=https://www.jax.org/strain/001800 | title=001800 - FVB Strain Details }}</ref> || 350 |- | 129S1/SvImJ || Agouti || [[Mutation|Targeted mutations]], [[cancer]]<ref name="auto5">{{cite web | url=https://www.jax.org/strain/002448 | title=002448 - 129S1 Strain Details }}</ref> || 222 |} ==== Jackson Labs DO project ==== [[File:PHYLOGENTIC TREE REDRAW.png|thumb|Phylogenetic tree of the eight founder strains used in the DO project, as well as their approximate age of divergence. M. spretus is included as an outgroup that diverged ~2 million years ago (mya), it is not part of the DO project.<ref>doi: 10.1007/s00335-015-9581-z</ref>]] The [[Jackson Laboratory|Jackson Labs]] DO ([[Outcrossing|Diversity Outbred]]) project<ref>{{cite web | url=https://www.jax.org/research-and-faculty/genetic-diversity-initiative | title=JAX Genetic Diversity Initiative (GeDI) }}</ref> is a mouse breeding program using multiple inbred founder strains to create a [[genetic diversity|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.<ref>{{cite journal | url=https://doi.org/10.1016/j.tig.2019.04.003 | doi=10.1016/j.tig.2019.04.003 | title=High-Diversity Mouse Populations for Complex Traits | year=2019 | last1=Saul | first1=Michael C. | last2=Philip | first2=Vivek M. | last3=Reinholdt | first3=Laura G. | last4=Chesler | first4=Elissa J. | last5=Chesler | first5=E. J. | journal=Trends in Genetics | volume=35 | issue=7 | pages=501–514 | pmid=31133439 | pmc=6571031 }}</ref> 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.<ref>{{cite journal | pmc=6571031 | year=2019 | last1=Saul | first1=M. C. | last2=Philip | first2=V. M. | last3=Reinholdt | first3=L. G. | author4=Center for Systems Neurogenetics of Addiction | last5=Chesler | first5=E. J. | title=High-diversity mouse populations for complex traits | journal=Trends in Genetics | volume=35 | issue=7 | pages=501–514 | doi=10.1016/j.tig.2019.04.003 | pmid=31133439 }}</ref> {| class="wikitable" |+ Founder strains used in the DO project ! Strain !! Derivation !! Subspecies origin !! Coat color<ref name="auto2"/> !! Common research uses !! Total Pubmed publications referencing the strain as of April 19, 2023 |- | A/J || Laboratory || ''Mus musculus domesticus''<ref name="auto3">{{cite journal | pmid=26135136 | year=2015 | last1=Morgan | first1=A. P. | last2=Welsh | first2=C. E. | title=Informatics resources for the Collaborative Cross and related mouse populations | journal=Mammalian Genome | volume=26 | issue=9–10 | pages=521–539 | doi=10.1007/s00335-015-9581-z | pmc=4633285 }}</ref> || Albino || [[Cancer]], [[immunology]]<ref>{{cite web | url=https://www.jax.org/strain/000646 | title=000646 - AJ Strain Details }}</ref> || 5,500 |- | [[C57BL/6|C57BL/6J]] || Laboratory || ''Mus musculus domesticus''<ref name="auto3"/> || Black || General purpose, background<ref name="auto1"/> || 25,723 |- | 129S1/SvImJ || Laboratory || ''Mus musculus domesticus'' || Agouti<ref name="auto5"/> || Targeted [[mutation]]s, [[cancer]]<ref name="auto5"/> || 222 |- | NOD/ShiLtJ || Laboratory || ''Mus musculus domesticus''<ref name="auto3"/> || Albino || Autoimmune [[type 1 diabetes]]<ref name="auto"/> || 105 |- | NZO/HILtJ || Laboratory || ''Mus musculus domesticus''<ref name="auto3"/> || Agouti || [[Obesity]]<ref>{{cite web | url=https://www.jax.org/strain/002105 | title=002105 - New Zealand Obese Strain Details }}</ref> || 11 |- | CAST/EiJ || Wild-derived || ''Mus musculus castaneus''<ref name="auto3"/> || Agouti || [[Mendelian inheritance|Crossbreeding heterozygous F1 hybrids]], [[genetic mapping]]<ref>{{cite web | url=https://www.jax.org/strain/000928 | title=000928 - CAST Strain Details }}</ref> || 154 |- | PWK/PhJ || Wild-derived || ''Mus musculus musculus'' <ref name="auto3"/> ||Agouti|| [[Genetic mapping]]<ref>{{cite web | url=https://www.jax.org/strain/003715 | title=003715 - Strain Details }}</ref> || 52 |- | WSB/EiJ || Wild-derived || ''Mus musculus domesticus''<ref name="auto3"/> || Agouti with head blaze, greyish coat || [[Genetic mapping]], [[evolution]]<ref>{{cite web | url=https://www.jax.org/strain/001145 | title=001145 - Strain Details }}</ref> || 65 |} == Appearance and behaviour == 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 of them; however, they are described below for two of the most commonly used strains. ===C57BL/6=== [[File:Black 6 mouse eating.jpg|thumb|A female C57BL/6 laboratory mouse]] {{main|C57BL/6}} 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]].<ref>{{cite web|url=http://www.cellmigration.org/resource/komouse/protocols/mouse_management_feb06.pdf|title=Aurora's Guide to Mo use Colony Management|vauthors=Connor AB|date=2006|work=Cell Migration Gateway|publisher=CMC Activity Center|access-date=19 December 2013|archive-date=23 September 2015|archive-url=https://web.archive.org/web/20150923201637/http://www.cellmigration.org/resource/komouse/protocols/mouse_management_feb06.pdf|url-status=dead}}</ref> 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.<ref>{{cite journal | vauthors = Garner JP, Weisker SM, Dufour B, Mench JA | title = Barbering (fur and whisker trimming) by laboratory mice as a model of human trichotillomania and obsessive-compulsive spectrum disorders | journal = Comparative Medicine | volume = 54 | issue = 2 | pages = 216–24 | date = April 2004 | pmid = 15134369 | url = http://www.dietvet-holistic.hu/download/ChR_2008/garner.cm.barberingepidemiology.pdf | url-status = dead | archive-url = https://web.archive.org/web/20131203003543/http://www.dietvet-holistic.hu/download/ChR_2008/garner.cm.barberingepidemiology.pdf | archive-date = 2013-12-03 }}</ref> 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. Also self-barbering can occur. Both hair and [[whiskers|vibrissae]] may be removed. Barbering is more frequently seen in female mice; male mice are more likely to display dominance through fighting.<ref>{{cite journal | vauthors = Sarna JR, Dyck RH, Whishaw IQ | title = The Dalila effect: C57BL6 mice barber whiskers by plucking | journal = Behavioural Brain Research | volume = 108 | issue = 1 | pages = 39–45 | date = February 2000 | pmid = 10680755 | doi = 10.1016/S0166-4328(99)00137-0 | s2cid = 18334770 | citeseerx = 10.1.1.519.7265 }}</ref> 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.<ref>{{cite journal | vauthors = Mogil JS, Wilson SG, Bon K, Lee SE, Chung K, Raber P, Pieper JO, Hain HS, Belknap JK, Hubert L, Elmer GI, Chung JM, Devor M | display-authors = 6 | title = Heritability of nociception I: responses of 11 inbred mouse strains on 12 measures of nociception | journal = Pain | volume = 80 | issue = 1–2 | pages = 67–82 | date = March 1999 | pmid = 10204719 | doi = 10.1016/s0304-3959(98)00197-3 | s2cid = 17604906 }}</ref> Unlike most laboratory mouse strains, the C57BL/6 drinks [[alcoholic beverage]]s voluntarily. It is more susceptible than average to [[morphine addiction]], [[atherosclerosis]], and age-related [[hearing loss]].<ref name="Trouble" /> When compared directly to BALB/c mice, C57BL/6 mice also express both a robust response to social rewards<ref>{{cite journal | vauthors = Panksepp JB, Lahvis GP | title = Social reward among juvenile mice | journal = Genes, Brain and Behavior | volume = 6 | issue = 7 | pages = 661–71 | date = October 2007 | pmid = 17212648 | pmc = 2040181 | doi = 10.1111/j.1601-183X.2006.00295.x | url = }}</ref><ref>{{cite journal | vauthors = Panksepp JB, Jochman KA, Kim JU, Koy JJ, Wilson ED, Chen Q, Wilson CR, Lahvis GP | display-authors = 6 | title = Affiliative behavior, ultrasonic communication and social reward are influenced by genetic variation in adolescent mice | journal = PLOS ONE | volume = 2 | issue = 4 | pages = e351 | date = April 2007 | pmid = 17406675 | pmc = 1831495 | doi = 10.1371/journal.pone.0000351 | bibcode = 2007PLoSO...2..351P | doi-access = free }}</ref> and empathy.<ref>{{cite journal | vauthors = Chen Q, Panksepp JB, Lahvis GP | title = Empathy is moderated by genetic background in mice | journal = PLOS ONE | volume = 4 | issue = 2 | pages = e4387 | date = 2009-02-11 | pmid = 19209221 | pmc = 2633046 | doi = 10.1371/journal.pone.0004387 | bibcode = 2009PLoSO...4.4387C | doi-access = free }}</ref> ===BALB/c=== {{main|BALB/c}} [[Image:Lightmatter lab mice.jpg|right|thumb|BALB/c laboratory mice]] 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]].<ref name="Festing">{{Cite web| title=BALB/c | work=Inbred Strains of Mice | publisher=Jackson Laboratory | url=http://www.informatics.jax.org/external/festing/mouse/docs/BALB.shtml | access-date=2007-04-16 }}</ref> 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.<ref>{{Cite web|title=BALB/cByJ |work=Jax Mice Data Sheet |publisher=Jackson Laboratory |url=http://jaxmice.jax.org/strain/001026_2.html |access-date=2007-04-16 |url-status=dead |archive-url=https://web.archive.org/web/20061116054205/http://jaxmice.jax.org/strain/001026_2.html |archive-date=November 16, 2006 }}</ref><ref>{{Cite web| title=BALB/cJ | work=Jax Mice Data Sheet | publisher=Jackson Laboratory | url=http://jaxmice.jax.org/strain/000651.html | access-date=2007-04-16 | archive-url= https://web.archive.org/web/20070411205957/http://jaxmice.jax.org/strain/000651.html| archive-date= 11 April 2007}}</ref> Male BALB/c mice are aggressive and will fight other males if housed together. However, the BALB/Lac substrain is much more docile.<ref name="aggressive">{{cite journal | vauthors = Southwick CH, Clark LH | year = 1966 | title = Aggressive behaviour and exploratory activity in fourteen mouse strains | journal = Am. Zool. | volume = 6 | page = 559 }}</ref> Most BALB/c mice substrains have a long reproductive life-span.<ref name="Festing"/> There are noted differences between different BALB/c substrains, though these are thought to be due to [[mutation]] rather than genetic contamination.<ref name="strains">{{cite book | vauthors = Hilgers J, van Nie R, Iványi D, Hilkens J, Michalides R, de Moes J, Poort-Keesom R, Kroezen V, von Deimling O, Kominami R | chapter = Genetic Differences in BALB/C Sublines | series = Current Topics in Microbiology and Immunology | display-authors = 6 | title = The BALB/C Mouse | volume = 122 | pages = 19–30 | year = 1985 | pmid = 2994956 | doi = 10.1007/978-3-642-70740-7_3 | isbn = 978-3-642-70742-1 }}</ref> The BALB/cWt is unusual in that 3% of progeny display true [[hermaphroditism]].<ref name="cWt">{{cite journal | vauthors = Eicher EM, Beamer WG, Washburn LL, Whitten WK | title = A cytogenetic investigation of inherited true hermaphroditism in BALB/cWt mice | journal = Cytogenetics and Cell Genetics | volume = 28 | issue = 1–2 | pages = 104–15 | year = 1980 | pmid = 7470243 | doi = 10.1159/000131518 }}</ref> ===Tg2576=== A useful model for [[Alzheimer's disease]] (AD) in the lab 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.<ref>{{cite web | url=https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/tg2576-mouse#:~:text=Tg2576%20mice%20exhibit%20many%20behavioral,70%2C%2072%E2%80%9375) | title=Tg2576 Mouse - an overview | ScienceDirect Topics }}</ref><ref>{{cite journal | doi=10.1007/s11357-021-00401-6 | title=Early manifestation of gait alterations in the Tg2576 mouse model of Alzheimer's disease | date=2021 | last1=Nyul-Toth | first1=Adam | last2=Delfavero | first2=Jordan | last3=Mukli | first3=Peter | last4=Tarantini | first4=Amber | last5=Ungvari | first5=Anna | last6=Yabluchanskiy | first6=Andriy | last7=Csiszar | first7=Anna | last8=Ungvari | first8=Zoltan | last9=Tarantini | first9=Stefano | journal=Geroscience | volume=43 | issue=4 | pages=1947–1957 | pmid=34160781 | pmc=8492885 }}</ref><ref>{{cite journal | url=https://www.sciencedirect.com/science/article/pii/S0197458022002536 | doi=10.1016/j.neurobiolaging.2022.11.017 | title=Neuronal hyperexcitability in the Tg2576 mouse model of Alzheimer's disease – the influence of sleep and noradrenergic transmission | date=2023 | last1=b. Szabo | first1=Anna | last2=Cattaud | first2=Vanessa | last3=Bezzina | first3=Charlotte | last4=Dard | first4=Robin F. | last5=Sayegh | first5=Fares | last6=Gauzin | first6=Sebastien | last7=Lejards | first7=Camille | last8=Valton | first8=Luc | last9=Rampon | first9=Claire | last10=Verret | first10=Laure | last11=Dahan | first11=Lionel | journal=Neurobiology of Aging | volume=123 | pages=35–48 | pmid=36634385 }}</ref> 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 a good model for early-stage AD because they show amyloidogenesis and working memory impairments linked to age but do not show neuronal degeneration.<ref name="Transgenic Mouse Models of Alzheime">{{cite journal | doi=10.3390/ijms23105404 | doi-access=free | title=Transgenic Mouse Models of Alzheimer's Disease: An Integrative Analysis | date=2022 | last1=Sanchez-Varo | first1=Raquel | last2=Mejias-Ortega | first2=Marina | last3=Fernandez-Valenzuela | first3=Juan Jose | last4=Nuñez-Diaz | first4=Cristina | last5=Caceres-Palomo | first5=Laura | last6=Vegas-Gomez | first6=Laura | last7=Sanchez-Mejias | first7=Elisabeth | last8=Trujillo-Estrada | first8=Laura | last9=Garcia-Leon | first9=Juan Antonio | last10=Moreno-Gonzalez | first10=Ines | last11=Vizuete | first11=Marisa | last12=Vitorica | first12=Javier | last13=Baglietto-Vargas | first13=David | last14=Gutierrez | first14=Antonia | journal=International Journal of Molecular Sciences | volume=23 | issue=10 | page=5404 | pmid=35628216 | pmc=9142061 | hdl=10261/306908 | hdl-access=free }}</ref> 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 the A246E FAD mutation. This crosses promotes the build-up of amyloid and plaque development in the CNS.<ref>{{cite web | url=https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/tg2576-mouse#:~:text=Tg2576%20mice%20exhibit%20many%20behavioral,70%2C%2072%E2%80%9375) | title=Tg2576 Mouse - an overview | ScienceDirect Topics }}</ref> 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 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.<ref name="Transgenic Mouse Models of Alzheime"/><ref>{{cite web | url=https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/tg2576-mouse#:~:text=Tg2576%20mice%20exhibit%20many%20behavioral,70%2C%2072%E2%80%9375) | title=Tg2576 Mouse - an overview | ScienceDirect Topics }}</ref> ==Husbandry== [[File:Lab mouse mg 3308.jpg|thumb|Laboratory mouse (note the [[Overview of discretionary invasive procedures on animals|ear tag)]]]] === Handling === 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.<ref>{{cite journal | vauthors = Hurst JL, West RS | title = Taming anxiety in laboratory mice | journal = Nature Methods | volume = 7 | issue = 10 | pages = 825–6 | date = October 2010 | pmid = 20835246 | doi = 10.1038/nmeth.1500 | s2cid = 6525713 }}</ref> Instead, handling mice using 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.<ref>{{cite journal | vauthors = Gouveia K, Hurst JL | title = Optimising reliability of mouse performance in behavioural testing: the major role of non-aversive handling | journal = Scientific Reports | volume = 7 | pages = 44999 | date = March 2017 | pmid = 28322308 | pmc = 5359560 | doi = 10.1038/srep44999 | bibcode = 2017NatSR...744999G }}</ref> === Nutrition === In nature, mice are usually [[herbivore]]s, consuming a wide range of fruit or grain.<ref name=ecodome>{{Cite web|url=https://www.qrg.northwestern.edu/projects/MarsSim/SimHTML/organisms/mouse.html|title=Mouse Info|website=www.qrg.northwestern.edu}}</ref> 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 {{convert|15|g|abbr=on}} per {{convert|100|g|abbr=on}} of body weight per day; water intake is approximately {{convert|15|ml|abbr=on}} per 100 g of body weight per day.<ref name=lvma>{{Cite web|url=http://www.lvma.org/mouse.html|archiveurl=https://archive.today/20120803201438/http://www.lvma.org/mouse.html|url-status=dead|title=Louisiana Veterinary Medical Association|archivedate=August 3, 2012}}</ref> ===Injection procedures=== [[Routes of administration]] of injections in laboratory mice are mainly [[subcutaneous administration|subcutaneous]], [[intraperitoneal administration|intraperitoneal]] and [[intravenous administration|intravenous]]. [[Intramuscular administration]] is not recommended due to small muscle mass.<ref name="duke">{{cite web|title=Guidelines for Selecting Route and Needle Size|url=http://vetmed.duhs.duke.edu/guidelines_for_needle_size_volume.htm|publisher=Duke University and Medical Center – Animal Care & Use Program|access-date=8 April 2011|archive-url=https://web.archive.org/web/20100609221642/http://vetmed.duhs.duke.edu/guidelines_for_needle_size_volume.htm|archive-date=9 June 2010}}</ref> [[Intracerebral administration]] is also possible. Each route has a recommended injection site, approximate [[Needle gauge comparison chart|needle gauge]] and recommended maximum injected volume at a single time at one site, as given in the table below: {|class="wikitable" ! [[Routes of administration|Route]] !! Recommended site<ref name="duke"/> !! [[Needle gauge comparison chart|Needle gauge]]<ref name=duke/> || Maximal volume<ref name=drexel>[http://www.drexelmed.edu/documents/ULAR/IACUC_drugs.pdf A Compendium of Drugs Used for Laboratory Animal Anesthesia, Analgesia, Tranquilization and Restraint] {{webarchive|url=https://web.archive.org/web/20110606212907/http://www.drexelmed.edu/documents/ULAR/IACUC_drugs.pdf |date=2011-06-06 }} at Drexel University College of Medicine. Retrieved April 2011</ref> |- | [[subcutaneous administration|subcutaneous]] || dorsum, between [[scapula]] || 25-26 [[Needle gauge comparison chart|ga]] || 2-3 [[millilitre|ml]] |- | [[intraperitoneal administration|intraperitoneal]] || [[left lower quadrant]] || 25-27 ga || 2-3 ml |- | [[intravenous administration|intravenous]] || [[lateral tail vein]]|| 27-28 ga || 0.2 ml |- | [[Intramuscular administration|intramuscular]] || hindlimb, caudal thigh || 26-27 ga || 0.05 ml |- | [[Intracerebral administration|intracerebral]]|| cranium || 27 ga |} To facilitate intravenous injection into the tail, laboratory mice can be carefully warmed under heat lamps to [[vasodilate]] the vessels.<ref name=duke/> ===Anaesthesia=== 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.<ref name=duke-anesthesia>[http://vetmed.duhs.duke.edu/guidelines_for_anesthetics_systemic_mouse.htm Guidelines for Systemic Anesthetics (Mouse)] From Duke University and Medical Center – Animal Care & Use Program. Retrieved April 2011</ref> It has a duration of effect of about 30 minutes.<ref name=duke-anesthesia/> ===Euthanasia=== Approved procedures for [[Animal euthanasia|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.<ref>{{cite web |url=http://www.theodora.com/rodent_laboratory/euthanasia.html |title=Euthanasia |work=Basic Biomethodology for Laboratory Mice |access-date=2012-10-17}}</ref> In 2013, the [[American Veterinary Medical Association]] issued new guidelines for {{CO2}} induction, stating that a flow rate of 10% to 30% volume/min is optimal for euthanasing laboratory mice.<ref name="2013 AVMA Guidelines for the Euthanasia of Animals: 2013 Edition">[https://www.avma.org/kb/policies/documents/euthanasia.pdf 2013 AVMA Guidelines for the Euthanasia of Animals]</ref> ==Pathogen susceptibility== A recent study detected a murine [[astrovirus]] in laboratory mice held at more than half of the US and Japanese institutes investigated.<ref>{{cite journal | vauthors = Ng TF, Kondov NO, Hayashimoto N, Uchida R, Cha Y, Beyer AI, Wong W, Pesavento PA, Suemizu H, Muench MO, Delwart E | display-authors = 6 | title = Identification of an astrovirus commonly infecting laboratory mice in the US and Japan | journal = PLOS ONE | volume = 8 | issue = 6 | pages = e66937 | year = 2013 | pmid = 23825590 | pmc = 3692532 | doi = 10.1371/journal.pone.0066937 | bibcode = 2013PLoSO...866937N | doi-access = free }}</ref> Murine astrovirus was found in nine mice strains, including [[NSG mouse|NSG]], [[NOD-SCID]], [[NSG-3GS]], [[C57BL6]]-''Timp-3<sup>−/−</sup>'', [[uPA-NOG]], [[B6J]], ICR, [[Bash2]], and [[BALB/C]], with various degrees of prevalence. The pathogenicity of the murine astrovirus was not known. ==Legislation in research== ===United Kingdom=== 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.<ref>{{cite web|url=https://www.societyofbiology.org/policy/policy-issues/biomedical-sciences/animal-research|title=Animal Research|last=Anon|work=Policy issues|publisher=Society of Biology|access-date=18 October 2014|archive-date=12 October 2014|archive-url=https://web.archive.org/web/20141012154350/https://www.societyofbiology.org/policy/policy-issues/biomedical-sciences/animal-research|url-status=dead}}</ref> Detailed data on the use of laboratory mice (and other species) in research in the U.K. are published each year.<ref>{{cite web|url=https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/212610/spanimals12.pdf|title=Annual Statistics of Scientific Procedures on Living Animals: Great Britain 2012|publisher=Home Office (UK)|year=2013|access-date=July 30, 2013}}</ref> 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.<ref name="ASPA statistics">{{cite web|url=https://www.gov.uk/government/statistics/statistics-of-scientific-procedures-on-living-animals-great-britain-2013|title=Annual Statistics of Scientific Procedures on Living Animals Great Britain 2013|last=Anon|date=2014|work=National statistics|publisher=Home Office|pages=26|access-date=18 October 2014}}</ref> ===United States=== In the U.S., laboratory mice are not regulated under the [[Animal Welfare Act of 1966|Animal Welfare Act]] administered by the [[United States Department of Agriculture|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, however, not a prerequisite for federal funding, unlike the actual compliance.<ref>{{cite web|url=http://grants.nih.gov/grants/olaw/references/phspol.htm |title=Office of Laboratory Animal Welfare: PHS Policy on Humane Care and Use of Laboratory Animals |publisher=Grants.nih.gov |access-date=2010-07-29}}</ref> ==Limitations== While mice are by far the most widely used animals in biomedical research, recent studies have highlighted their limitations.<ref name="nytimes.com">{{cite news| vauthors = Kolata G |title=Mice Fall Short as Test Subjects for Some of Humans' Deadly Ills|work=The New York Times |url=https://www.nytimes.com/2013/02/12/science/testing-of-some-deadly-diseases-on-mice-mislead-report-says.html?_r=0|access-date=6 August 2015|agency=New York Times|date=11 February 2013}}</ref> For example, the utility of rodents in testing for [[sepsis]],<ref name="Mouse Models of Sepsis and Septic">{{cite journal | vauthors = Korneev KV | title = [Mouse Models of Sepsis and Septic Shock] | journal = Molekuliarnaia Biologiia | volume = 53 | issue = 5 | pages = 799–814 | date = 18 October 2019 | pmid = 31661479 | doi = 10.1134/S0026893319050108 | doi-access = free }}</ref><ref name="pnas.org">{{cite journal | vauthors = Seok J, Warren HS, Cuenca AG, Mindrinos MN, Baker HV, Xu W, Richards DR, McDonald-Smith GP, Gao H, Hennessy L, Finnerty CC, López CM, Honari S, Moore EE, Minei JP, Cuschieri J, Bankey PE, Johnson JL, Sperry J, Nathens AB, Billiar TR, West MA, Jeschke MG, Klein MB, Gamelli RL, Gibran NS, Brownstein BH, Miller-Graziano C, Calvano SE, Mason PH, Cobb JP, Rahme LG, Lowry SF, Maier RV, Moldawer LL, Herndon DN, Davis RW, Xiao W, Tompkins RG | display-authors = 6 | title = Genomic responses in mouse models poorly mimic human inflammatory diseases | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 110 | issue = 9 | pages = 3507–12 | date = February 2013 | pmid = 23401516 | pmc = 3587220 | doi = 10.1073/pnas.1222878110 | bibcode = 2013PNAS..110.3507S | doi-access = free }}</ref> [[burn]]s,<ref name="pnas.org"/> [[inflammation]],<ref name="pnas.org"/> [[stroke]],<ref>{{cite journal | vauthors = Ramsay I | title = Attempted prevention of neonatal thyrotoxicosis | journal = British Medical Journal | volume = 2| issue = 6048| date = December 1976 | page = 1385 | pmid = 1000245| pmc = 1690299| doi = 10.1136/bmj.2.6048.1385-a }}</ref><ref name="The Trouble With Animal Models">{{cite news| vauthors = Gawrylewski A |title=The Trouble With Animal Models|url=http://www.the-scientist.com/?articles.view/articleNo/25184/title/The-Trouble-with-Animal-Models/|access-date=6 August 2015|agency=The Scientist|date=1 July 2007}}</ref> [[Amyotrophic lateral sclerosis|ALS]],<ref>{{cite journal | vauthors = Benatar M | title = Lost in translation: treatment trials in the SOD1 mouse and in human ALS | journal = Neurobiology of Disease | volume = 26 | issue = 1 | pages = 1–13 | date = April 2007 | pmid = 17300945 | doi = 10.1016/j.nbd.2006.12.015 | s2cid = 24174675 }}</ref><ref name="nature.com">{{cite news| vauthors = Hayden EC |title=Misleading mouse studies waste medical resources|url=http://www.nature.com/news/misleading-mouse-studies-waste-medical-resources-1.14938|access-date=6 August 2015|agency=Nature|date=26 March 2014}}</ref><ref name="ReferenceA">{{cite news| vauthors = Perrin S |title=Preclinical research: Make mouse studies work|url=http://www.nature.com/news/preclinical-research-make-mouse-studies-work-1.14913|access-date=6 August 2015|agency=Nature|date=26 March 2014}}</ref> [[Alzheimer's disease]],<ref>{{cite journal | vauthors = Cavanaugh SE, Pippin JJ, Barnard ND | title = Animal models of Alzheimer disease: historical pitfalls and a path forward | journal = Altex | volume = 31 | issue = 3 | pages = 279–302 | date = 10 April 2013 | pmid = 24793844 | doi = 10.14573/altex.1310071 | doi-access = free }}</ref> [[diabetes]],<ref>{{cite journal | vauthors = Roep BO, Atkinson M, von Herrath M | title = Satisfaction (not) guaranteed: re-evaluating the use of animal models of type 1 diabetes | journal = Nature Reviews. Immunology | volume = 4 | issue = 12 | pages = 989–97 | date = December 2004 | pmid = 15573133 | doi = 10.1038/nri1502 | s2cid = 21204695 }}</ref><ref>{{cite journal | vauthors = Chandrasekera PC, Pippin JJ | title = Of rodents and men: species-specific glucose regulation and type 2 diabetes research | journal = Altex | volume = 31 | issue = 2 | pages = 157–76 | date = 21 November 2013 | pmid = 24270692 | doi = 10.14573/altex.1309231 | doi-access = free }}</ref> [[cancer]],<ref>{{cite journal | vauthors = Begley CG, Ellis LM | title = Drug development: Raise standards for preclinical cancer research | journal = Nature | volume = 483 | issue = 7391 | pages = 531–3 | date = March 2012 | pmid = 22460880 | doi = 10.1038/483531a | s2cid = 4326966 | bibcode = 2012Natur.483..531B | doi-access = free }}</ref><ref>{{cite journal | vauthors = Voskoglou-Nomikos T, Pater JL, Seymour L | title = Clinical predictive value of the in vitro cell line, human xenograft, and mouse allograft preclinical cancer models | journal = Clinical Cancer Research | volume = 9 | issue = 11 | pages = 4227–39 | date = September 2003 | pmid = 14519650 | url = http://clincancerres.aacrjournals.org/content/9/11/4227.full.pdf }}</ref><ref>{{cite journal | vauthors = Dennis C | title = Cancer: off by a whisker | journal = Nature | volume = 442 | issue = 7104 | pages = 739–41 | date = August 2006 | pmid = 16915261 | doi = 10.1038/442739a | s2cid = 4382984 | bibcode = 2006Natur.442..739D | doi-access = free }}</ref><ref>{{cite journal | vauthors = Garber K | title = Realistic rodents? Debate grows over new mouse models of cancer | journal = Journal of the National Cancer Institute | volume = 98 | issue = 17 | pages = 1176–8 | date = September 2006 | pmid = 16954466 | doi = 10.1093/jnci/djj381 | doi-access = free }}</ref><ref>{{cite news| vauthors = Begley S |title=Rethinking the war on cancer|url=http://www.newsweek.com/rethinking-war-cancer-88941|access-date=6 August 2015|agency=Newsweek|date=5 September 2008}}</ref> [[multiple sclerosis]],<ref name="ReferenceB">{{cite news| vauthors = Bolker J |title=There's more to life than rats and flies|url=http://www.nature.com/articles/491031a.epdf|access-date=6 August 2015|agency=Nature|date=1 November 2012}}</ref> [[Parkinson's disease]],<ref name="ReferenceB"/> and other illnesses has been called into question by 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.<ref name="nytimes.com"/> 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]], 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 [[Interleukin 8|IL-8]], [[IL-37]], [[TLR10]], [[ICAM3|ICAM-3]], etc.<ref name="Mouse Models of Sepsis and Septic"/> 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 the [[microbiota]], which directly affects the immune system and the development of pathological conditions. Moreover, persistent virus infections (for example, [[Herpesviridae|herpesviruses]]) are activated in humans, but not in [[specific-pathogen-free|SPF]] mice with [[Sepsis|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 the overwhelming majority of studies, while the [[human population]] is heterogeneous, pointing to the importance of studies in interstrain hybrid, [[outbred]], and nonlinear mice.<ref name="Mouse Models of Sepsis and Septic"/> An article in ''[[The Scientist (magazine)|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 the design and execution of the tests themselves.<ref name="The Trouble With Animal Models"/> 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.<ref>{{cite journal | vauthors = Lahvis GP | title = Unbridle biomedical research from the laboratory cage | journal = eLife | volume = 6 | pages = e27438 | date = June 2017 | pmid = 28661398 | doi = 10.7554/eLife.27438 | pmc = 5503508 | url = | veditors = Shailes S | doi-access = free }}</ref> 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.<ref>{{Cite web|title=The inescapable problem of lab animal restraint {{!}} Garet Lahvis {{!}} TEDxMtHood – YouTube|url=https://www.youtube.com/watch?v=2Q1aDrGRlrU|access-date=2020-11-30|website=www.youtube.com| date=5 December 2019 }}</ref> 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.<ref>{{cite journal | vauthors = Cressey D | title = Fat rats skew research results | journal = Nature | volume = 464 | issue = 7285 | pages = 19 | date = March 2010 | pmid = 20203576 | doi = 10.1038/464019a | doi-access = free }}</ref> Many laboratory animals, including mice, are chronically stressed, which can also negatively affect research outcomes and the ability to accurately extrapolate findings to humans.<ref>{{cite journal | vauthors = Balcombe JP, Barnard ND, Sandusky C | title = Laboratory routines cause animal stress | journal = Contemporary Topics in Laboratory Animal Science | volume = 43 | issue = 6 | pages = 42–51 | date = November 2004 | pmid = 15669134 }}</ref><ref>{{cite journal | vauthors = Murgatroyd C, Patchev AV, Wu Y, Micale V, Bockmühl Y, Fischer D, Holsboer F, Wotjak CT, Almeida OF, Spengler D | display-authors = 6 | title = Dynamic DNA methylation programs persistent adverse effects of early-life stress | journal = Nature Neuroscience | volume = 12 | issue = 12 | pages = 1559–66 | date = December 2009 | pmid = 19898468 | doi = 10.1038/nn.2436 | s2cid = 3328884 }}</ref> Researchers have also noted that many studies involving mice are poorly designed, leading to questionable findings.<ref name="The Trouble With Animal Models"/><ref name="nature.com"/><ref name="ReferenceA"/> 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 a 2014 study from [[McGill University]] which suggests that mice handled by men rather than women showed higher stress levels.<ref>{{cite journal | vauthors = Sorge RE, Martin LJ, Isbester KA, Sotocinal SG, Rosen S, Tuttle AH, Wieskopf JS, Acland EL, Dokova A, Kadoura B, Leger P, Mapplebeck JC, McPhail M, Delaney A, Wigerblad G, Schumann AP, Quinn T, Frasnelli J, Svensson CI, Sternberg WF, Mogil JS | display-authors = 6 | title = Olfactory exposure to males, including men, causes stress and related analgesia in rodents | journal = Nature Methods | volume = 11 | issue = 6 | pages = 629–32 | date = June 2014 | pmid = 24776635 | doi = 10.1038/nmeth.2935 | s2cid = 8163498 }}</ref><ref name="economist.com"/><ref>{{Cite journal| vauthors = Katsnelson A |title=Male researchers stress out rodents|url=http://www.nature.com/news/male-researchers-stress-out-rodents-1.15106|journal=Nature|doi=10.1038/nature.2014.15106|year=2014|s2cid=87534627|doi-access=free}}</ref><ref>{{Cite news|url=https://www.science.org/content/article/male-scent-may-compromise-biomedical-research|title=Male Scent May Compromise Biomedical Research|date=2014-04-28|newspaper=Science {{!}} AAAS|access-date=2017-01-10}}</ref> Another study in 2016 suggested that gut [[Microbiota|microbiome]]s in mice may have an impact upon scientific research.<ref>{{Cite news|url=https://www.science.org/content/article/mouse-microbes-may-make-scientific-studies-harder-replicate|title=Mouse microbes may make scientific studies harder to replicate|date=2016-08-15|newspaper=Science {{!}} AAAS|access-date=2017-01-10}}</ref> ==Market size== 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.<ref>{{cite news | vauthors = Einhorn B |url=https://www.bloomberg.com/news/articles/2019-04-01/china-s-demand-for-17-000-gene-altered-lab-mice-is-skyrocketing |title=China's Selling Genetically-Modified Mice for $17,000 a Pair |work=[[Bloomberg News]] |date=2019-04-01 |access-date=2019-04-02 }}</ref> == See also == * [[Woolly mouse]] * [[Laboratory rat]] * [[Animal testing]] * [[Animal testing on rodents]] * [[Animal model]] * [[Animal identification]] * [[Fe, Fi, Fo, Fum, and Phooey]], five laboratory mice who orbited the Moon 75 times on [[Apollo 17]] * [[Mouse models of colorectal and intestinal cancer]] * ''[[Pinky and the Brain]]'' * [[Testing cosmetics on animals]] * ''[[Monument to the laboratory mouse]]'' *[[TetTag]] == References == {{Reflist|30em}} == Further reading == {{Refbegin}} * {{cite book | vauthors = Musser GG, Carleton MD |chapter=Superfamily Muroidea |editor=Wilson, D.E. |editor2=Reeder, D.M. |title=Mammal Species of the World: a taxonomic and geographic reference |publisher=Johns Hopkins University Press |location=Baltimore |year=2005 |isbn=978-0-8018-8221-0 |pages=894–1531 |chapter-url=http://www.bucknell.edu/msw3 |edition=3rd }} * {{cite book | vauthors = Nyby J |chapter=Ch. 1 Auditory communication in adults |editor=Willott, James F. |title=Handbook of Mouse Auditory Research: From Behavior to Molecular Biology |url=https://archive.org/details/handbookmouseaud00will |url-access=limited |publisher=CRC Press |location=Boca Raton |year=2001 |pages=[https://archive.org/details/handbookmouseaud00will/page/n17 3]–18 |isbn=9780849323287 }} {{Refend}} == External links == {{Commons category|Lab mice}} {{Wikispecies|Mus musculus}} '''Taxonomy''' * [http://www.findmice.org/ FindMice.org] '''Genetics''' * [http://www.ensembl.org/Mus_musculus/ Ensembl Mus musculus genome browser], from the [[Ensembl]] Project * [http://vega.sanger.ac.uk/Mus_musculus Vega Mus musculus genome browser], includes NOD mouse sequence and annotation '''Media''' * [http://www.digimorph.org/specimens/Mus_musculus/ Pictures, movies and applets showing the anatomy of ''Mus musculus''], from www.digimorph.org * [http://mednews.wustl.edu/news/page/normal/6040.html 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 * {{Cite web |date=2019-04-15 |title=It's just in mice! This scientist is calling out hype in science reporting |url=https://www.statnews.com/2019/04/15/in-mice-twitter-account-hype-science-reporting/ |website=[[Stat (website)|STAT]] |language=en-US}} * [https://web.archive.org/web/20080509105126/http://www.arkive.org/species/ARK/mammals/Mus_musculus/ Arkive] Photographs.Short text. * [https://web.archive.org/web/20190621124504/http://brainmaps.org/ High-Resolution Brain Maps and Brain Atlases of ''Mus musculus''] '''Further reading''' * [https://archive.today/20120803201438/http://www.lvma.org/mouse.html Biology of the Mouse], from the Louisiana Veterinary Medical Association * [http://www.nature.com/nature/mousegenome/ Nature Mouse Special 2002] * [https://web.archive.org/web/20050313011817/http://www.ahsc.arizona.edu/uac/notes/classes/rodentbio/rodentbio.html Biology of Laboratory Rodents] by David G. Besselsen {{Model Organisms}} {{Murinae (Melasmothrix–Mus)}} {{Authority control}} [[Category:Cosmopolitan mammals]] [[Category:House mouse]] [[Category:Laboratory mice| ]] [[Category:Old World rats and mice]] [[Category:Cruelty to animals]] [[Category:Animal models]]
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