Guidelines for Nomenclature of Mouse and Rat Strains

Congenic Strains GuidelinesforNomenclatureofMouseandRatStrains Revised:September2010 InternationalCommitteeonStandardizedGeneticNomenclatureforMice Chairperson:Dr.JananT.Eppig (e-mail:[email protected]) RatGenomeandNomenclatureCommittee Chairperson:Dr.GoranLevan (e-mail:[email protected]) In2001,theInternationalCommitteeonStandardizedNomenclatureforMiceandtheRatGenomeand NomenclatureCommitteeagreedtoestablishajointsetofrulesforstrainnomenclature,applicable tostrainsofbothspecies.Theserewrittenguidelinesreflectthiscollaboration,inadditionto documentingnewandrevisedrulesforthenamingofstrains.Thisdocumentisupdatedannuallyby theinternationalnomenclaturecommitteesformouseandrat. ReferencetoformerversionsoftherulesformousestrainnomenclaturecanbefoundinSnell (1941),CommitteeforStandardizedGeneticNomenclatureinMice(1952,1960,1976,1981,1989, 1996),Festing(1979,1993),Staats(1986),Maltaisetal.(1997).Arecentsummaryofmouseguidelineswaspublishedin2006(Eppig2006).ReferencetoformerrulesforratstrainnomenclaturecanbefoundinCommitteeonRatNomenclature(1992). Anarchivedversionofthepreviousonlineguide(January2009)isavailablehere. Currentnomenclaturerulesfornaminggenesareavailableonlineat: Formouse:http://www.informatics.jax.org/mgihome/nomen/gene.shtml#genenom Forrat:http://rgd.mcw.edu/nomen_rules.html TableofContents 1.   Introduction 1.1  Mice 1.2  Rats 2.  Laboratorycodes 3.  InbredStrainsandHybrids 3.1  Definition 3.2  NomenclatureofInbredStrains 3.3  IndicationofInbreeding 3.4  Substrains 3.5  Hybrids 4.  StrainsMadefromMultipleInbredStrains 4.1  RecombinantInbredStrains 4.2  MixedInbredStrains 4.3  RecombinantCongenicStrains 4.4  AdvancedIntercrossLines 5.  Coisogenic,Congenic,andSegregatingInbredStrains 5.1  CoisogenicStrains 5.2  CongenicStrains 5.3  ChromosomeSubstitutionorConsomicStrains 5.3.1  ConsomicStrains 5.4  SegregatingInbredStrains 5.5  ConplasticStrains 6.  OutbredsandClosedColonies 6.1  Outbreds 6.2  ClosedColonies 7.  References 1.   Introduction Miceandratsusedinthelaboratoryderivefromavarietyofsources.Productionofinbred strainsmeansthatthesebackgroundscanbedefinedandthusrequirenomenclatureconventions.It shouldbeborneinmindthatgeneticdriftmeansthattheremaystillbeunknowngeneticdifferences betweenindividualswithinstrains. 1.1   Mice MostlaboratorymicehavecontributionsfrombothMusmusculusmusculusandMus musculusdomesticus.ThereisevidencethatsmallercontributionsalsomayhavecomefromMus musculusmolossinusandMusmusculuscastaneus.Therefore,theyshouldnotbe referredtobyspeciesname,butratheraslaboratorymiceorbyuseofaspecificstrainorstock name.(Inaddition,somerecentlydevelopedlaboratorymousestrainsarederivedwhollyfromother Musspeciesorothersubspecies,suchasM.spretus). MousestrainnamesshouldberegisteredthroughtheMouseGenomeDatabase(MGD)at http://www.informatics.jax.org/mgihome/submissions/amsp_submission.cgi. 1.2   Rats LaboratoryratstrainsderivefromtheRattusnorvegicusspecies.Anotherspecies, Rattusrattus,alsoisusedasanexperimentalmodel,buthasnotcontributedtothecommon laboratoryratstrains. RatstrainnamesshouldberegisteredthroughtheRatGenomeDatabase (RGD)athttp://rgd.mcw.edu. 2.   Laboratorycodes AkeyfeatureofmouseandratnomenclatureistheLaboratoryRegistrationCode orLaboratorycode,whichisacodeofusuallythreetofourletters(firstletter uppercase,followedbyalllowercase)thatidentifiesaparticularinstitute, laboratory,orinvestigatorthatproduced,andmayholdstocksof,amouseor ratstrain.SubstrainsshouldbeidentifiedbyLaboratorycodes,asshouldcongenic andotherstrainswhereseveraldifferentformsexistthatarenototherwise distinguishable.LaboratorycodesareassignedbytheInstituteofLaboratoryAnimal Research(ILAR)(http://dels-old.nas.edu/ilar_n/ilarhome/register_lc.php). ExamplesofLaboratorycodesare: JTheJacksonLaboratory RlW.L.andL.B.Russell JrJohnRapp McwMedicalCollegeofWisconsin KyoKyotoUniversity 3.   InbredStrainsandHybrids 3.1   Definition Strainscanbetermedinbrediftheyhavebeenmatedbrotherxsisterfor20ormoreconsecutive generations,andindividualsofthestraincanbetracedtoasingleancestralpairatthe 20thorsubsequentgeneration.Atthispointtheindividuals'genomeswillonaverage haveonly0.01residualheterozygosity(excludinganygeneticdrift)andcanberegardedformost purposesasgeneticallyidentical.Inbredstrainsmustbecontinuouslymatedbrotherxsister(or equivalent)thereafter. Otherbreedingschemescanbeusedtoproduceinbredstrains;consecutiveparentxoffspringmatingmaybeused,providedthattheyoungeroftheparentsisalwaysused(i.e.,theoffspringthatismatedtoparentissubsequentlymatedtoitsoffspring).Otherbreedingschemesareacceptableprovidedthattheinbreedingisequivalentto20successivegenerationsofsibmating(Green1981). 3.2   NomenclatureofInbredStrains Aninbredstrainshouldbedesignatedbyauniquebriefsymbolmadeup ofuppercase,Roman,letters,oracombinationoflettersandnumbers beginningwithaletter.(Notethatsomepre-existingstrainsdonotfollow thisconvention;e.g.,mousestrain129P1/J). Careshouldbetakenthatmouseandratstrainsdonotoverlapinstraindesignations.(Note:afewhistoricalexamplesexistofsimilarmouseandratstraindesignationsandtheseareallowedtostand,withtheirsubstraindesignations identifyingthemasunique). Inbredstrainsthathaveacommonorigin,butareseparatedbeforeF20arerelatedinbredstrains,andsymbolsshouldreflectthisrelationship. Examples: Mousestrains:NZB,NZC,NZO Ratstrains:SR,SS 3.3   IndicationofInbreeding Thenumberofbrotherxsisterinbreedinggenerationscanbeindicated,ifnecessary,byadditioninparenthesesofFfollowedbythenumberofgenerations. Example: Ratstrain:ACI/N(F159) Ifthereisnotinformationastothetotalnumberofgenerations,butaminimumnumberofrecent inbreedinggenerationsisknown,thiscanbeshownbyaquestionmark+theknownnumberof subsequentgenerationsofinbreeding. Example: Mousestrain:C3H/HeJ-ruf(F?+25) 3.4   Substrains Establishedinbredstrainsmaygeneticallydivergewithtimeintosubstrains,duetoanumberofcircumstances: Iftwobranchesareseparatedafter20butbefore40generationsof inbreedingtherestillwillbeenoughresidualheterozygositythattwo geneticallydifferentsubstrainswillresult(Green1981). Ifbranchesareseparatedformorethan20generationsfromacommon ancestor,itislikelythatgeneticvariationbetweenthebrancheswillhave occurredbymutationandgeneticdrift. Ifgeneticdifferencesareprovenbygeneticanalysistohaveoccurred betweenbranches. Substrainsaregiventherootsymboloftheoriginalstrain,followedbyaforwardslashandasubstraindesignation.ThedesignationisusuallytheLaboratorycodeoftheindividualorlaboratoryoriginatingthestrain. Examples: IS/KyoSubstrainofISratstrainoriginatingatKyotoUniversity. A/HeSubstrainofAmousestrainoriginatingfromWalterHeston. Ifalaboratoryoriginatesmorethanonesubstrain,serialnumbersshouldbeaddedtotheLaboratorycode. Example: Mousestrains:FL/1Re,FL/2Re (Notethathistoricalexceptionstothisruleexist;forexample,inmouse,BALB/cisnota substrain,DBA/1andDBA/2areseparatestrainsandarenotsubstrains.) Substrainsmaygiverisetofurthersubstrainsbycontinuedmaintenancebyadifferent investigatororthroughestablishmentofanewcolony.Inaddition,substrainsariseifdemonstrable geneticdifferencesfromtheoriginalsubstrainarediscovered.Ineithercase,furthersubstrain designationsareadded,withouttheadditionofanotherslash. Examples: C3H/HeHMousesubstrainderivedatHarwell(H)fromtheHeston(He)substrainofC3H. SR/JrIpcvRatsubstrainderivedatInstituteofPhysiology,CzechAcademyofSciences(Ipcv)fromtheJohnRapp(Jr)substrainofSR Laboratorycodesshouldbeaccumulatedbecausegeneticdifferenceswillaccumulatewithtime, theratedependingtosomeextentonvaryinglevelsofqualitycontrolatthefacilitiesthathave housedandbredthestrainorsubstrain.Organizationsdistributingmiceandratsshouldinclude thenumberofgenerationsthestrainhasbeenseparatedfromtheparentstrainintheinformation theyprovideregardingthestrain.Strainnamescanbeabbreviatedinpublicationsafterthefirst mentionofthefullproperdesignation. 3.5   Hybrids Miceorratsthataretheprogenyoftwoinbredstrains,crossedinthesamedirection,are geneticallyidentical,andcanbedesignatedusinguppercaseabbreviationsofthetwoparents (maternalstrainlistedfirst),followedbyF1.NotethatreciprocalF1hybridsarenotgenetically identical,andtheirdesignationsare,therefore,different. Examples: D2B6F1MousethatistheoffspringofaDBA/2motherandC57BL6/Jfather.AfullF1designationis(DBA/2NxC57BL/6J)F1. B6D2F1Mousethatistheoffspringofthereciprocalcross.AfullF1designationis(C57BL/6JxDBA/2N)F1. CB1BD22F1Mousethatistheoffspringoftworecombinantinbredstrains,aCXB1motherandBXD22father;fullF1designationis(CXB1/ByJxBXD22/TyJ)F1. Furthercrossesproduceoffspringthatarenolongergeneticallyidentical,butitmay stillbeappropriatetogivethemdesignationsreflectingtheirparentage,similartothoseforF1hybrids. Examples: D2B6F2areoffspringofaD2B6F1intercross. B6(D2AKRF1)areoffspringofa(DBA/2xAKR/J)F1male backcrossedtoaC57BL/6Jfemale. Inalltheabovecases,forclarity,thefullstrainsymbolsshouldbegivenin anypublicationwhenthehybridsorcrossesarefirstreferredto.Ifahybrid isconstructedusingasubstrainknowntodifferfromthe"standard" straingeneticallyand/orphenotypically,thesubstrainshouldbeindicatedin thehybridsymbol;e.g.,BALB/cBy=CBy,C3H/HeSn=C3Sn. Approvedabbreviationsforcommonmousestrainsarelistedbelow: 129   129strains(mayincludesubtype,e.g.,129S6forstrain129S6/SvEvTac) A   Astrains AK   AKRstrains B   C57BL B6   C57BL/6strains B10   C57BL/10strains BR   C57BR/CD C   BALB/cstrains C3   C3Hstrains CB   CBA D1   DBA/1strains D2   DBA/2strains HR   HRS/J L   C57L/J R3   RIIIS/J J   SJL SW   SWR 4.   StrainsMadefromMultipleInbredStrains Miceorratscanbeproducedthathaveadefinedgeneticbackground, derivedfromtwoormoreinbredstrains,andthatmayormaynotbegenetically identical.Suchanimalsshouldbedesignatedappropriately,accordingtothe breedingschemethatproducedthem. 4.1   RecombinantInbredStrains Recombinantinbred(RI)strainscontainunique,approximatelyequalproportionsofgeneticcontributionsfromtwooriginalprogenitorinbredstrains.Traditionally,recombinantinbred(RI)strainsareformedbycrossinganimalsoftwoinbredstrains,followedby20ormoreconsecutivegenerationsofbrotherxsistermatings(Bailey1971,Taylor1978).Alternatebreedingschemescanbeused,suchascreatingRIstrainsetsfromAdvancedIntercrossLines,whereF2animalsarenonsibmatedforseveralgenerations,followedultimatelyby20ormoreconsecutivegenerationsofbrotherxsistermatings.Notethatifbackcrossingtooneoftheparentalstrainsisinvolved,thiswillcreaterecombinantcongenicstrainsandshouldbenamedaccordingly.RIstrainsshouldbedesignatedbyuppercaseone-ortwo-letterabbreviationsofbothparentalstrainnames,withthefemalestrainwrittenfirst,andseparatedbyanuppercaseletterXwithnointerveningspaces.AllmembersofRIsetsinvolvingthesametwostrainswillbeseriallynumberedregardlessofwhethertheywerecreatedinoneormorelaboratories.SequentialnumbersmaybeobtainedfromMGD(emailto:[email protected]). Examples: CXBRecombinantinbredmousestrainderivedfromacrossofBALB/cxC57BL/6J. MultipleRIstrainsderivedfromthesamestrainprogenitorsaregivenserialnumbers. Examples: BXD1,BXD2,BXD3MembersoftheBXDsetofmouseRIstrainsderivedfromacrossofC57BL/6xDBA/2. HXB1,HXB2,HXB3MembersoftheHXBsetofratRIstrainsderivedfromacrossofSHR/OlaIpcvxBN-Lx/Cub. Ifthesecondstrainabbreviationendsinanumber(e.g.,CX8RIstrains),ahyphenshouldbeusedtoseparateitfromtheserialnumber(e.g.,CX8-1). Recombinantinbredstrainsmaybeintercrossedformappingcomplextraits.SuchF1sarecalledrecombinantinbredintercrosses(RIX)andaresymbolizedthesameasF1sbetweenotherinbredstrains Example: (BXD1/TyXAXB19/Pgn)F1AnF1betweenafemaleBXD1/TyandamaleAXB19/Pgn. 4.2   MixedInbredStrains Incipientinbredstocksorinbredstrainsthatarederivedfromonlytwoparentalstrains(oneofwhichcouldbeagene-targetedEScellline)canbedesignatedusinguppercaseabbreviationsforthetwostrains,separatedbyasemicolon.Thestraindesignationprecedingthesemicolonshouldbethehostandthestrainfollowingthesemicolonthedonor,specificallyfortargetedmutationswherethedonoristheEScellline.Whenthetwoprogenitorstrainsdonothaveadonor/hostrelationship,theconventionfollowedisthesameaswhenconstructingaF1hybriddesignation;thatis,theabbreviationofthestrainfromwhichthefemaleoriginatedinthefirstcrossisgivenbeforethesemicolon.Laboratorycodesandserialnumbersshouldbeusedtodistinguishstrainsproducedindifferentlaboratories,ormultiplestrainsfromthesamelaboratory.Becausethesedesignationsmaybeusedforamixedstockbeforeitisfullyinbred,thesestocksshouldnotbeassumedtobeinbredunlessaccompaniedbyaninbreedinggeneration number(e.g.,>F20). Example: B6;129-Acvr2tm1ZukAmixedstrainderivedfromC57BL/6Janda129EScelllinecarryingatargetedknockoutoftheAcvr2gene. Amutantstrain,incipientorinbred,derivedfrommorethantwoprogenitorstrainsorhavinggeneticcontributionfromanunknownsourceisconsidereda"mixed"inbredandmaybedesignatedasSTOCKfollowedbyaspace(i.e.,nohyphen)andthemutation(s)orchromosomeanomalyitcarries. Example: STOCKRb(16.17)5BnrAninbredstrainofunknownorcomplex backgroundcarryingtheRobertsoniantranslocationRb(16.17)5Bnr. Oncesuchamutantstockachievesinbredstatus,itshouldbegiventheappropriatestraindesignation.Itmaybedesignatedusingthesymbolsforthegeneticmutationsitcarriesinall uppercase,providedthesymbolsareshort.Becausethechangeinstrainnameisoptional,thoughstronglyrecommended,somestrainsdesignatedasSTOCKmaybeinbred. Example: JIGR/DnAninbredstraindevelopedfromamixedbackgroundstockcarryingthemutationgr(grizzled)andtheji(jittery)alleleofAtcay. WhenamutantalleleorchromosomalaberrationismaintainedbycrossinganimalsbearingthemutationtoanF1hybridateverygenerationoratalternategeneration(s),thestockisdesignatedbythesymbolthatwouldbeusedforthatF1,butwithoutthe"F1"suffix,andfollowedbytheappropriatealleleorchromosomeanomalysymbol. Examples: B6C3Fea/a-DhTheDh(dominanthemimelia)mutationismaintainedbycrossingtoa(B6C3Fea/a)F1ateachgeneration,butthestockitselfisnotanF1. 4.3   RecombinantCongenicStrains RecombinantCongenic(RC)Strainsareformedbycrossingtwoinbredstrains,followedbyafew(usuallytwo)backcrossesofthehybridstooneoftheparentalstrains(the"recipient"strain),withsubsequentinbreedingwithoutselectionforanyspecificmarkers(DemantandHart,1986).Suchinbredstrainswillconsistofthebackgroundrecipientstraingenomeinterspersedwithhomozygoussegmentsofthedonor(theamountofdonorstraingenomedependingonthenumberoforiginalbackcrosses,2backcrosseswillgiveonaverage12.5%). RCStrainsshouldberegardedasfullyinbredwhenthetheoreticalcoefficientofinbreedingapproximatesthatofastandardinbredstrain.Forthispurpose,onegenerationofbackcrossingwillberegardedasbeingequivalenttotwogenerationsofbrotherxsistermating.Thus,astrainproducedbytwobackcrosses(N3,equivalenttoF6)followedby14generationsofbrotherxsistermating(F14)wouldbefullyinbred. RCstrainsshouldbedesignatedbyanuppercaseabbreviationofthetwostrains,recipientstrainlistedfirst,separatedbylowercase"c." Example: CcSRecombinantcongenicstrainbetweenBALB/crecipientandSTSdonor. MultipleRCstrainsderivedfromthesamestrainprogenitorsaregivenserialnumbers. Example: CcS1,CcS2,CcS3,etc. Ifthesecondstrainabbreviationendsinanumber(e.g.,129P2),ahyphenshouldbeusedtoseparateitfromtheserialnumber. 4.4   AdvancedIntercrossLines Advancedintercrosslines(AIL)aremadebyproducinganF2generationbetweentwoinbredstrains andthenintercrossingineachsubsequentgeneration,butavoidingsiblingmatings(DarvasiandSoller,1995).Thepurposeistoincreasethepossibilityoftightlylinkedgenesrecombining. ThesymbolsshouldcontaintheLaboratorycodeofthelaboratorythathasproducedtheline, followedbyacolon,thetwoinbredstrainabbreviations,separatedbyacomma,withthegeneration numberincludedinthesymbolfollowingahyphen.GenerationsaredesignatedG3,G4,etc.beginning withthefirstnon-sibcrossaftertheF2generation. Example: Pri:B6,D2-G#ThisisanAILstockcreatedat PrincetonfromtheinbredstrainsC57BL/6xDBA/2.TheGnumberwillincrease witheachgeneration. 5   Coisogenic,Congenic,andSegregatingInbredStrains Thereareseveralwaysinwhichinbredstrainsmaydifferatonlyasmallpartofthegenome. 5.1   CoisogenicStrains Coisogenicstrainsareinbredstrainsthatdifferatonlyasinglelocusthroughmutation occurringinthatstrain.StrainscontainingtargetedmutationsinEScellsthatarethencrossed to,andmaintained,onthesameinbredsubstrainfromwhichtheEScellswerederivedcanbe regardedascoisogenic,butthepossibilityofmutationselsewhereshouldbeconsidered.Similarly, chemicallyorradiationinducedmutantsonaninbredbackgroundcanbeconsideredcoisogenic, althoughothergenomicalterationscouldbepresent.Acoisogenicstrainmayaccumulategenetic differencesovertimebygeneticdriftunlessperiodicallybackcrossedtotheparentalstrain. Coisogenicstrainsshouldbedesignatedbythestrainsymbol(andwhereappropriatethesubstrainsymbol)followedbyahyphenandthegenesymbolofthedifferentialallele,initalics. Example: 129S7/SvEvBrd-Fyntm1SorAtargetedmutationoftheFyngenewasproducedusingtheAB1EScelllinederivedfrom129S7/SvEvBrd.Chimericanimalswerematedto129S7/SvEvBrdandtheallelesubsequentlymaintainedonthiscoisogenicstrain. Example: C57BL/6JEi-tthThetremorwithtiltedheadmutationintheC57BL/6JEistrain. Insomecases,suchmutationswillbemaintainedinheterozygouscondition.Itshouldbenoted thatthismeansthatthestraindesignationdoesnotreflectthebreedingsystem,norindicatethe specificgenotypeofagivenmouseorrat. Example: C57BL/6J-Aqp2cphThecongenitalprogressivehydronephrosismutationintheaquaporin2genearoseontheC57BL/6Jstrain.Itisacoisogenicstrain,butbecausehomozygotesaregenerally juvenilelethal,thestrainismaintainedbybreedingheterozygotesAqp2cph/+x Aqp2cph/+. Ifthenumberofgenerationsofinbreedingsincethemutationaroseinacoisogenicstrainisto beshown,itcanbeindicatedbyaddingthenumberofgenerationssincethemutationtothenumber before: Example: F110+F23indicates23generationsofbrotherxsistermatingssincetheoccurrenceofa mutationatF110inaninbredstrain. 5.2   CongenicStrains Congenicstrainsareproducedbyrepeatedbackcrossestoaninbred(background)strain,with selectionforaparticularmarkerfromthedonorstrain(Snell1978,Flaherty1981).Congeniclinesthatdifferatahistocompatibilitylocusandthereforeresisteachother'sgraftsarecalledcongenicresistant(CR)lines. Astraindevelopedbythismethodisregardedascongenicwhenaminimumof10backcrossgenerationstothebackgroundstrainhavebeenmade,countingthefirsthybridorF1generationasgeneration1.Atthispointtheresidualamountofunlinkeddonorgenomeinthestrainislikelytobelessthan0.01.(Notethattheamountofdonorgenomelinkedtotheselectedgeneormarkerisreducedatamuchslowerrate,approximatelyequivalentto200/N,whereNisthenumberofbackcrossgenerationsforN>5(Flaherty1981;Silver1995). Markerassistedbreedingormarkerassistedselectionbreeding,alsoknownas"speedcongenics"permitstheproductionofcongenicstrainsequivalentto10backcrossgenerationsinasfewas5generations.(Markeletal.,1997;Wakelandetal.,1997).Providedthattheappropriatemarkerselectionhasbeenused,thesearetermedcongenicstrainsifthedonorstraincontributionunlinkedtotheselectedlocusorchromosomalregionislessthan0.01.Ideally,descriptionsofspeedcongenicstrainsinfirstpublicationsthereofshouldincludethenumberandgenomicspacingofmarkersusedtodefinethecongenicityofthestrain.Becausespeedcongenicsdependuponthoroughmarkeranalysisandcanvarybyparticularexperimentalprotocol,theinbredstatusofspeedcongenicsshouldberegardedwithcaution. Congenicstrainsaredesignatedbyasymbolconsistingofthreeparts.Thefullorabbreviatedsymboloftherecipientstrainisseparatedbyaperiodfromanabbreviatedsymbolofthedonorstrain,thisbeingthestraininwhichthealleleormutationoriginated,whichmayormaynotbeitsimmediatesourceinconstructingthecongenicstrain.(Incaseswherethechromosomeonwhichthemutationaroseisunknown,e.g.,thedonorisnotinbredoriscomplexoranF1hybrid,thesymbolCgshouldbeusedtodenotecongenic.TheuseofthedonorstrainsymbolorCgisessentialtodistinguishcongenicfromcoisogenicstrains.Cgisalsousedtodesignateastrainconstructedbycrossingtogethertwocongenicstrainsthathavebeenbackcrossedseparatelytothesamehostbackground,butwheretheirrespectivedonorstrainsdiffer.Cgisalsoappliedwhereallelesoriginatefromasingledonorstrain,butthecongenicstrainalsocarriesothercoisogenicalleles.Ineachcase,theuseofCgindicatesthatallelesinthestrainnamecamefrommorethanonesource).Ahyphenthenseparatesthestrainnamefromthesymbol(initalics)ofthedifferentialallele(s)introgressedfromthedonorstrain. Examples: B6.AKR-H2kAmousestrainwiththegeneticbackgroundofC57BL/6butwhichdiffersfromthatstrainbytheintroductionofadifferentialallele(H2k)derivedfromstrainAKR/J. LEW.BN-RT1nAratstrainwiththegeneticbackgroundofLEWbutwhichdiffersfromthatstrainbytheintroductionofadifferentialsegment(RT1n)derivedfromstrainBN. DA.F344-Cia5AratstrainwiththegeneticbackgroundofDAontowhichasegmentfromtheF344straincontainingtheCia5QTLhasbeentransferred. B6.Cg-KitW-44JGpi1aAmousestrainwiththegeneticbackgroundofC57BL/6,butwherethedonorstrainismixed,theKitalleleoriginatingfromC3H/HeJandtheGpi1alleleoriginatingfromCAST/Ei. Ifseverallinesderivedfromthesamehostbackgroundanddonorstrainsandcarryingthesamedifferentialallele(s)areavailable,theindividuallinesshouldbedistinguishedbyaddingaforwardslashfollowedbyserialnumbersandLaboratorycodes. Examples: C.B10-H2b/1Sn C.B10-H2b/2Sn Parenthesesmaybeusedtoshowthataninbred,incipientcongenicorcongenicinbredstrainmayhaveaminor contributionfromoneotherstrain. Examples: B6(C)-mutAmutationoriginatesonaninbred(e.g.,C57BL/6J),iscrossedouttoorontoanotherbackground(e.g.,BALB/c)andtheniscrossedbackontotheoriginalbackground. C.129P(B6)-Il2tm1HorAtargetedmutationcreatedina129EScelllineandtransferredfromaB6;129PmixedbackgroundtoBALB/c. B6(C)-mutAmutationarisesonacongenicstraincarryinganothermutation(e.g.,B6.C-m)andtheoriginalmutationisbredoutofthenewstrain.Noteiftheoriginalmutationisnotprovedtoberemovedfromthestrain,thesymbolwouldbeB6.Cm-mut. B6(C)-mutAmutationarisesonahybridormixedbackgroundstock(e.g.,B6CF1)andisbackcrossedontooneoftheoriginalinbredstrains(e.g.,C57BL/6J). B6.C(Cg)-mutAmutationhasbeenbackcrossedfromonestrain(e.g.,BALB/c)ontoanother(e.g.,C57BL/6J)butaroseonamixedbackgroundorhashadavariedhistoryandtheoriginofthechromosomalsegmentisunknown. IfthechromosomalsegmentthathasbeentransferredisdefinedbyseveralgenesormultipleDNAloci,thesegmentcanbedefinedinthesymbolbylistingthemostproximalandthemostdistalmarkersdemonstratedtobeinthesegmentinparentheses,separatedbyahyphen. Examples: B6.Cg-(D4Mit25-D4Mit80)/LtAcongenicstrainmadebyintroducingintoC57BL/6Jasegmentofchromosome4fromanoutbredormixedstrain(=Cg),extendingbetweenthetwodefinedmarkers. B6.CBA-(D4Mit25-D4Mit80)/LtAsimilarcongenicstraininwhichthedonorchromosomalsegmentcomesfromtheCBA/Jstrain. Notethatthemarkersdefiningthesegmentonlydescribethemostproximalanddistalmarkerstested,andthisdoesnotimplythattherearenototheruntestedmarkersfurtherproximalordistal.Ifseverallinesaremade,inthesameordifferentlabsthatcontainthesamesegmentandwouldbeotherwiseindistinguishable,thenaforwardslash,serialnumberandLaboratorycodeshouldbeappended. Ifnecessary,thenumberofbackcrossgenerationsshouldbeindicatedbyNandthenumberinparenthesesfollowingthestrainname;generationsshouldnotbeincorporatedintothestrainname.IncipientcongenicsmaybegivencongenicnomenclatureatN5,aslongasthenumberofgenerationsofbackcrossingisclearlydocumentedininformationaccompanyingthestrain.Incaseswhereitisnecessarytousemorecomplexmatingsystems,thegenerationsshouldbeexpressedasNequivalents(NE)andthestrainregardedascongenicataminimumofNE10.Forexample,whenbackcrossingarecessivegeneontoaninbredbackground,after10roundsofbackcrossingandintercrossingtorecoverahomozygoteforthenextbackcross(20generations),thestrainwouldbeatNE10.Whenacongenicstrainismaintainedbybrotherxsistermatingsafterbackcrossing,thenumberofbrotherxsistergenerationsfollowsthenumberofbackcrossgenerations,e.g.,(N10F6),10generationsofbackcrossingfollowedby6generationsofbrotherxsisterinbreeding;(NE12F17),acomplexsystemofbackcrossesandintercrossesgeneticallyequivalentto12backcrosses,followedby17generationsofbrotherxsistermatings. WhengeneratingspeedcongenicsNwillbelessthan10initially,neverthelesstheactualnumbershouldbegiveninparenthesesfollowingtheN,e.g.,N(6),andthedetailsofbreedingsystemandmarkersuseddetailedelsewhereinapublicationordatabase. 5.3   ChromosomeSubstitutionorConsomicStrains Chromosomesubstitutionorconsomicstrains(Nadeauetal.,2000)areproducedbyrepeatedbackcrossingofawholechromosomeoritspartsontoaninbredstrain.Thetermchromosomesubstitutionstrainisacommondesignationforconsomic,subconsomic,andconplasticstrains.Tocreateachromosomesubstitutionstrain,transferofawholechromosomeoralargechromosomalregioniscarriedout,whileincongenicstrains,thetransferredentityisagene,markerorgenomicsegmentincludingaspecificmarkerorinterval. 5.3.1   ConsomicStrains Consomicstrainsareproducedbyrepeatedbackcrossingofawholechromosomeontoaninbredstrain.Aswithcongenicstrains,aminimumof10backcrossgenerationsisrequired,countingtheF1generationasgeneration1.Forautosomesitisnecessarytogenotypeprogenytoensurethattheselecteddonorchromosomehasnotrecombinedwiththecorrespondingrecipientchromosome.ThegenericdesignationforconsomicstrainsisHOSTSTRAIN-Chr#DONORSTRAIN. Examples: SHR-ChrYBNInthisconsomicratstrain,theYchromosomefromBNhasbeenbackcrossedontoSHR. C56BL/6J-Chr19SPR Inthisconsomicmousestrain,aM.spretusChromosome19hasbeenbackcrossedontoC57BL/6J. C56BL/6J-Chr1A/JChr3DBA/2JInthisconsomicmousestrain,Chromosome1fromtheA/JstrainandChromosome3fromtheDBA/2J strainhavebeenbackcrossedontoC57BL/6J. Experienceshowsthatonoccasionitisimpossibletotransferanentirechromosomefromonestraintoanotherduetolethaleffectsonaparticularchromosome.Forexample,aconsomicsetonwhichPWD/PhindividualchromosomesweretransferredtoC57BL/6JrevealedthatChr11andChrXcannotbetransferredintact.Todesignate"sections"oftransferredchromosomesthatcontributetoaconsomicset,regionscanbeindicatedasadecimal1,2,3,etc. Thus,apartofChr11ofthisconsomicsetwouldbe:C57BL/6J-Chr11.1PWD/Ph/ForeJ. Althoughconsomicstrainsaresimilarinconceptanddevelopmenttocongenicstrains,in consomicnomenclaturethenameofthehoststrainisnotabbreviated,andnoperiodfollowedbythe donorstrainisrequiredbecausethestrainoforiginisshowninthesuperscript.Capitalizationofalllettersinthesuperscriptandnon-italicizationofthechromosomeletter/numberandofthesuperscriptdistinguishachromosomeidentifierfromanallelesymbol. 5.4   SegregatingInbredStrains Segregatinginbredstrainsareinbredstainsinwhichaparticularalleleormutationismaintainedinheterozygousstate.Theyaredevelopedbyinbreeding(usuallybrotherxsistermating)butwithheterozygosityselectedateachgeneration.Theyaredesignatedlikeotherinbredstrainssincethesegregatinglocusispartofthestandardgenotypeofthestrain(seeSection5.1CoisogenicStrains).Whensegregatingcoatcolorallelesarepartoftheinbredstrain's normalphenotype,theyneednotbeincludedinthestrainname(seeexamplesbelow).Detailsofinbredstraingenotypesareavailableinpublicationsanddatabases. Examples: 129P3/JThismousestrainsegregatesforthetyrosinaseallelesalbino(Tyrc)andchinchilla(Tyrc-ch). WB/ReThismousestrainsegregatesforthedominantwhitespottingalleleofthekitoncogene(KitW). Strainsthatcarrylinkedallelesincouplingorrepulsionshouldbedesignatedsothatitisclearthattheallelesarelinkedandthephaseofthelinkedgenesisspecified. Examples: B6.Cg-mLeprdb/++InthisstrainthemandLeprdballelesarecarriedononechromosome(incoupling)andthewildtypeallelesontheother. B6.Cg-m+/+LeprdbInthisstrainthemandLeprdballelesarecarriedondifferenthomologsofthechromosome(inrepulsion);thisisalsocalledabalancedstrain. 5.5   ConplasticStrains Conplasticstrainsarestrainsinwhichthenucleargenomefromonestrainhasbeencrossedontothecytoplasmofanother,i.e.,themitochondrialdonorisalwaysthefemaleparentduringthebackcrossingprogram.ThedesignationisNUCLEARGENOME-mtCYTOPLASMICGENOME. Example: C57BL/6J-mtBALB/cAstrainwiththenucleargenomeofC57BL/6Jandthecytoplasmic(mitochondrial)genomeofBALB/c. SuchastrainisdevelopedbycrossingmaleC57BL/6JmicewithBALB/cfemales,followedby repeatedbackcrossingoffemaleoffspringtomaleC57BL/6J.Aswithcongenicstrains,aminimumof 10backcrossgenerationsisrequired,countingtheF1generationasgeneration1. 6.   OutbredsandClosedColonies 6.1   Outbreds Outbredstocksaregeneticallyundefined;thatis,notwoindividualsfromanoutbredstockarethesame.Outbredsareintentionallynotbredwithsiblingsorcloserelatives,asthepurposeofanoutbredstockistomaintainmaximumheterozygosity.Oneadvantageofusingoutbredstocksislowercost,becauseoutbredshaverelativelylonglifespan,areresistanttodisease,andhavehighfecundity.Theyareusefulforexperimentationwheregenotypeisunimportantandwherearandomgeneticpopulationisdesired.Foroutbreds,thecommonstrainrootisprecededbytheLaboratoryCodeoftheinstitutionholdingthestock. Examples: Tac:ICRTheICRoutbredstockmaintainedbyTaconicFarms,Inc. Hsd:NIHSwissTheNIHSwissoutbredstockmaintainedbyHarlanSpragueDawley,Inc. 6.2ClosedColonies Aclosedcolonycontainslimitedgeneticdiversity,andismaintainedneitherbysib-mating(inbred),norbyselectivematingtomaximizeheterozygosity(outbred).Allmatingsoccurwithinthecolonymembers,butbreedersneednotbeselectedfromspecificparentage.Noanimalsareintroducedintothecolonyfromoutsidethestockfromgenerationtogeneration. Closedcoloniesmaybeestablishedasawaytomorereadilymaintainadifficultmutation,wherethedesireistomaintainareasonablyuniformbackground,butpoormatingperformanceprohibitsuseofsib-matingschemes.Notethatclosedcoloniesdescribeapermanentmatingsystemandthisdoesnotapply,forexample,ifaninbredstrainisout-crossedtoanearrelativeinasinglegenerationbecauseofatemporarybreedingcrisis. Closedcolonydesignationsconsistofthestrainoforiginandappropriatelydesignatedmutations(ifapplicable),followedby[cc]toindicateclosedcolony. Example: C57BL/6Tac-Bmp4tm1Blh[cc]AclosedcolonyofmiceoriginatingfromtheC57BL/6TacinbredstrainandcarryingtheBmp4tm1Blhtargetedmutation. 7.   References   Bailey,D.W.1971.Recombinantinbredstrains,anaidtofindingidentity,linkage,andfunctionofhistocompatibilityandothergenes.Transplantation11:325-327. CommitteeonRatNomenclature.1992.Definition,nomenclature,andconservationofratstrains.ILARNews34:S1-S26. CommitteeonStandardizedGeneticNomenclatureforMice.1952.Standardizednomenclatureforinbredstrainsofmice.CancerRes.12:602-613. CommitteeonStandardizedGeneticNomenclatureforMice.1960.Standardizednomenclatureforinbredstrainsofmice,secondlisting.CancerRes.20:145-169. CommitteeonStandardizedGeneticNomenclatureforMice.1976.Nomenclatureforinbred strainsofmicepreservedbyfreezing.MouseNewsLett54:2-3. 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