Editing Laboratory mouse (section)

==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 &#124; 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
|}