Nomenclature of Genetically Engineered and Mutant Mice - JAX

Transgenic mice carry a segment of foreign DNA incorporated into their genome via non-homologous recombination (e.g., pronuclear microinjection), infection with ... 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Geneticsvs.genomics Ethicalconsiderations Personalizedmedicineandyou WhatisCRISPR? MiceinBiomedicalResearch AreasofResearch Addiction Aging Alzheimer's&OtherDementias Cancer Diabetes Microbiome Rarediseases Vision ClinicalKnowledgebase MaineCancerGenomicsInitiative News  JAXNews JAXBlog MinutetoUnderstanding Subscribe PressRoom TheSearchMagazine ExplorebyTopic AboutUs  FastFacts OurPeople&Culture OurValues Diversity,Equity&Inclusion FacesofJAX OurLeaders WorkWithUs OurCampuses&Communities OurImpact CollaborationatJAX OurMedicalImpact OurEconomicImpact OurCommunityImpact OurEnvironmentalImpact OurHistory Careers ContactUs Give JAXHome JAX®MiceandServices CustomerSupport TechnicalSupport NomenclatureofGeneticallyEngineeredandMutantMice Geneticallyengineeredmicehaveinducedmutations,includingtransgenes,targetedmutations(knockoutsorknockins),andretroviral,proviralorchemicallyinducedmutations. TransgenicmicecarryasegmentofforeignDNAincorporatedintotheirgenomevianon-homologousrecombination(e.g.,pronuclearmicroinjection),infectionwitharetroviralvectororhomologousinsertion. Targetedmutantmiceareproducedbyfirstinducinggenedisruptions,replacementsorduplicationsintoembryonicstem(ES)cellsviahomologousrecombinationbetweentheexogenous(targeting)DNAandtheendogenous(target)gene.ThegeneticallymodifiedEScellsarethenmicroinjectedintohostembryosattheeight-cellblastocyststage.Theseembryosaretransferredtopseudopregnanthostfemales,whichthenbearchimericprogeny.Thechimericprogenycarryingthetargetedmutationintheirgermlinearethenbredtoestablishaline.Ifthenewlyestablishedlinehasadisruptedordeletedgene,itiscalledaknockout;ifithasaneworduplicatedgene,itiscalledaknockin. Micewithchemicallyinducedmutationsareproducedbyusingavarietyofchemicals.Onepopularchemicalmutagen,ethylnitrosourea(ENU),isusedtoinducepointmutations.ENUmutagenesisinvolvesexposingmalemicetoENUandthenmatingthetreatedmalestountreatedfemales.Theresultantprogeny,manyofwhichcarrypointmutations,arescreenedforphenotypesofinterest. Applications Geneticallyengineeredmiceareusefulforelucidatingbasicbiologicalprocesses,studyingrelationshipsbetweengenemutationsanddiseasephenotypes,andmodelinghumandisease.ResearchapplicationsareincludedonstraindatasheetsintheJAX®MiceDatabase.Theapplicationsarecompiledusinganumberofinformationsources(pleaserefertoMouseInformationResources),buttheyarenotall-inclusive:rapidlyadvancingbiomedicalresearchcontinuallyuncoversnewapplicationsandusesforgeneticallyengineeredandmutantmicestrains. Some geneticallyengineeredandmutantmicestrainshaveamutationassociatedwithaspecifichumandisease.Ifthegeneormutationisorthologoustothatinhumansandcausesthesamediseaseinhumans,thestrainisdesignatedasamodelofthehumandisease.Manifestationofthegeneticmutation(phenotypicexpression)maydifferbetweenhumansandmice.Investigatorsarestronglyencouragedtoresearchrecommendedmousemodelstobesuretheyareappropriatefortheirresearch. Nomenclatureforgeneticallyengineeredmice Nomenclatureforchemicallyinducedandtargetedmutationsfollowthesameguidelinesasdescribedformicewithspontaneousmutations.Genesymbolsareitalicized.Symbolsforrecessivegenesbeginwithalowercaseletter,andsymbolsfordominant,semi-dominant,andco-dominantgenesbeginwithanuppercaseletter,followedbylowercaseletters.Thegeneandallelesymbolsformutantgenesarethesameuntilthegeneiscloned. Allelesaredesignatedeitherbythechemicalmutagenorbytheabbreviation“tm”(targetedmutation),followedbyanumberandthelaboratoryregistrationcode,andselectioncriteriasuperscriptedtothegenesymbol(e.g.,Apoa1tm1Unc). Controlsforgeneticallyengineeredmice Ifamutationismaintainedonastandardinbredbackground,thatinbredstrainistheappropriatecontrol.Ifamutationismaintainedoneitheramixedorsegregatinggeneticbackground,wild-typemice(phenotypicallynon–mutantmice)fromthecolonyarethebestcontrols.However,becausemanyofourgeneticallyengineeredstrainsaremaintainedbyhomozygousmatings,wild-typecontrolsfromthecolonyarenotavailable.F2hybridsareoftenusedasapproximatephysiologicalcontrolsforstrainscarryingtargetedmutations(knockouts)maintainedonamixedC57BL/6x129background(designatedB6;129).TheF2generationisproducedbyF1xF1matings.ThegeneticbackgroundofC57BL/6Jx129F2micevariesamonglittermatesbecauseofgenesegregationfromtheF1hybridparents.AlthoughtheseF2miceareonlyanapproximategeneticmatchtotheB6;129background,theydocontainonlygenesderivedfromeithertheC57BL/6or129geneticbackgrounds.WecurrentlydistributetwoC57BL/6Jx129F2hybrids,differingprimarilyintheir129substrainprogenitor: B6129PF2/J(Stocknumber100903) Parentalstrains:C57BL/6J-Aw–J and129P3/J(formerly129/J). SuggestedcontrolforstrainsdesignatedB6;129P. B6129SF2/J(Stocknumber101045) Parentstrains:C57BL/6Jand129S1/SvImJ(formerly129S3/SvImJ). SuggestedcontrolforstrainsdesignatedB6;129S. Thecontrolsnotedinthestraindetailsformicecarryingtargetedmutationsareselectedtomostappropriatelymatchthe129strainusedtoderivetheEScelllines(Simpson etal.1997). Note:TheB6129F1hybridsareusuallylessappropriatecontrolsthanaretheF2hybridsbecausetheparentalallelesofF1micearenotsegregatingasopposedtothoseonamixedB6;129background. 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