Three ways a B6J mouse differs from B6N and why it should ...

C57BL/6J mice have a naturally occurring in-frame five-exon deletion in Nnt that removes exons 7–11 and results in inappropriate glucose ... 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Howeverinthemanydecadesthatthisstrainhasbeendistributed,anumberofdifferentsubstrainsofC57BL/6havearisenfromtheoriginalC57BL/6J(B6J),suchasC57BL/6NJ(B6N).Thesesubstrains(designatedbythelabcodeafterthe6)differgeneticallyasaresultofaccumulatedspontaneousmutationsovertime.SincetheC57BL/6strainissocommonlyusedasthebackgroundstrainformanydifferenttargetedmutations,itisimportanttoknowwhichsubstrainofB6youareusingandnottousedifferentsubstrainsinterchangeably. Ifyoudon’ttakethesedifferencesintoconsiderationandcontrolfortheminyourexperimentaldesign,yourinterpretation ofkeyexperimentsmaybewrong,costingyouvaluabletimeandresources,andjeopardizingthereproducibilityofyourwork. HerearethreewaysinwhichB6JmicedifferfromB6Nmice: 1.MiceontheC57BL/6NgeneticbackgroundcarrytheCrb1mutation. Photoreceptordegenerationisobservedinspots,causedbyretinalfoldsandpseudorosettes,foundinthefundusoftheeyeofallvendorlinesoftheC57BL/6Nline(Mattapalliletal.2012).TheC57BL/6Jstraindoesnotcarrytherd8mutation.Therefore,ifyouareusingmicethatarerequiredtointerpretvisualcuesorifyouarecharacterizinganewmutationthatisexpectedtoaffectvision,usingmicewiththeB6Nbackgroundcaninterferewithyourexperiments. 2.B6JmicehaveamutationintheNntgenethatmayaffectmetabolism. Nicotinamidenucleotidetranshydrogenase(Nnt)gene,locatedonmousechromosome13,encodesamitochondrialproteininvolvedinβ-cellmitochondrialmetabolism.C57BL/6Jmicehaveanaturallyoccurringin-framefive-exondeletioninNntthatremovesexons7–11andresultsininappropriateglucosehomeostasisinmaleB6Jmice.B6Jmicehaveanormallifespanandactuallyhavearobustweightgainanddevelopobesityandinsulinresistanceonahighfatdiet(Nicholson,etal.2010).C57BL/6Nlinesdonothavethismutation.PreviousstudiesfromJAXscientistDr.EdwardLeiterlookedintotheeffectoftheNntalleleondietinducedobesity(DIO)responsivenesscomparingB6JmalestoB6Nmales.Dr.LeitershowedthatB6JmaleshadasignificantlymorerobustDIOresponse(higherweightgain,moreadiposityandmoresevereimpairedglucosetolerance)thanB6/NJmales. 3.OneB6substraincarriesadeletioninSnca–thegenethatencodesalphasynuclein–thatisfrequentlyinvolvedinpeoplewithParkinson’sdisease. C57BL/6JOlaHsdmicecarryadeletioninSncathatisnotpresentinanyotherB6substrains.Thismutationhasnotbeenshowntoalterspatiallearningandmemory;however,itcouldimpactstudiesonParkinson’sdisease. UsingthewrongB6substraincanaffectreproducibilityandchangeyourdatainterpretation. Appreciatingtheimpactgeneticbackgroundandinparticularthesubstrainyouareusinghasinyourresearch,canbecriticalforgeneratingqualitydataandreproducibleresearchresults.Infact,onepublicationdescribeshowmispairingsubstrainsofB6miceoccursoftenandmayleadtoinaccurateandconflictingfindings.Inastudyofacetaminophen-inducedliverinjury,thechoiceofB6controlsdramaticallychangedtheinterpretationofthephenotypeinaJnkknockoutmousefromhepatoprotectivetohepatotoxic!Whencomparedtocontrolmiceofthewrongsubstrain,theKOmutationappearedtohaveaprotectiveeffectbutwhencomparedtotheappropriatesubstrain,theoppositewastrue(Bourdietal.2011).SotakenoteoftheB6substrainyouareworkingwithandmakesureyouareusingtheappropriatecontrols! NotsurewhichB6substrainyourKOmutationortransgeneison? YoucanhaveyourmiceevaluatedusingtheC57BL/6SubstrainCharacterizationPanel. 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