Genetic and Molecular Analysis of Wild-Derived Arrhythmic Mice 英文参考文献.docVIP

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Genetic and Molecular Analysis of Wild-Derived Arrhythmic Mice 英文参考文献.doc

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Genetic and Molecular Analysis of Wild-Derived Arrhythmic Mice 英文参考文献

GeneticandMolecularAnalysisofWild-Derived ArrhythmicMice TsuyoshiWatanabe1,TohruSuzuki1,2,AkiraIshikawa3,YukiYokota1,HirokiR.Ueda4,5,RikuhiroG. Yamada4,HajimeTei6,SakiImai1,ShigeruTomida1,JunyaKobayashi1,EmikoNaito1,ShinobuYasuo1, NobuhiroNakao1,TakaoNamikawa3,TakashiYoshimura1,ShizufumiEbihara1* 1Division of Biomodeling, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan, 2Department ofInfectiousDisease, Hamamatsu University SchoolofMedicine,Hamamatsu,Japan,3DivisionofAppliedGeneticsandPhysiology,GraduateSchoolofBioagriculturalSciences,NagoyaUniversity,Nagoya,Japan, 4Laboratory for Systems Biology, Center for Developmental Biology, RIKEN, Hyogo, Japan, 5Functional Genomics Subunit,Center for Developmental Biology, RIKEN, Hyogo,Japan,6ResearchGroupofChronogenomics,MitsubishiKagakuInstituteofLifeSciences,Tokyo,Japan Abstract Anewcircadianvariantwasisolatedbyscreeningtheintercrossoffspringofwild-caughtmice(Musmusculuscastaneus). Thisvariantwascharacterizedbyaninitialmaintenanceofdampedoscillationsandsubsequentlossofrhythmicityafter beingtransferredfromlight-dark(LD)cyclestoconstantdarkness(DD).Tomapthegenesresponsibleforthepersistenceof rhythmicity(circadianratio)andthelengthoffree-runningperiod(t),quantitativetraitlocus(QTL)analysiswasperformed usingF2miceobtainedfromanF1crossbetweenthecircadianvariantandC57BL/6Jmice.Asaresult,asignificantQTLwith amaineffectforcircadianratio(Arrhythmicity;Arrh-1)wasmappedonChromosome(Chr)8.Fort,foursignificantQTLs, Shortfree-runningperiod(Sfp-1)(Chr1),Sfp-2(Chr6),Sfp-3(Chr8),Sfp-4(Chr11)weredetermined.Anepistaticinteraction was detected between Chr 3 (Arrh-2) and Chr 5 (Arrh-3). An in situ hybridization study of clock genes and mouse Period1::luciferase (mPer1::luc) real-time monitoring analysis in the suprachiasmatic nucleus (SCN) suggested that arrhythmicity in this variant might not be attributed to core circadian mechanisms in the SCN neurons. Our strategy usingwild-derivedvariantmicemayprovideanovel