Origins of Albino and Hooded Rats Implications from Molecular Genetic Analysis across Modern Laboratory Rat Strains 英文参考文献.docVIP

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Origins of Albino and Hooded Rats Implications from Molecular Genetic Analysis across Modern Laboratory Rat Strains 英文参考文献.doc

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Origins of Albino and Hooded Rats Implications from Molecular Genetic Analysis across Modern Laboratory Rat Strains 英文参考文献

OriginsofAlbinoandHoodedRats:Implicationsfrom MolecularGeneticAnalysisacrossModernLaboratory RatStrains TakashiKuramoto1*,SatoshiNakanishi1,MasakoOchiai2,HitoshiNakagama2,BirgerVoigt1, TadaoSerikawa1 1InstituteofLaboratoryAnimals,GraduateSchoolofMedicine,KyotoUniversity,Sakyo-ku,Kyoto,Japan,2NationalCancerCenterResearchInstitute,Chuo-ku,Tokyo, Japan Abstract Albinoandhooded(orpiebald)ratsareoneofthemostfrequentlyusedlaboratoryanimalsforthepast150years.Despite thisfact,theoriginofthealbinomutationaswellasthegeneticbasisofthehoodedphenotyperemainedunclear.Recently, thealbinomutationhasbeenidentifiedastheArg299HismissensemutationintheTyrosinasegeneandthehooded(H) locus has been mapped to the ,460-kb region in which only the Kit gene exists. Here, we surveyed 172 laboratory rat strains for the albino mutation and the hooded (h) mutation that we identified by positional cloning approach to investigate possible genetic roots and relationships of albino and hooded rats. All of 117 existing laboratory albino rats sharedthesamealbinomissensemutation,indicatingtheyhadonlyonesingleancestor.Geneticfinemappingfollowedby denovosequencingofBACinsertscoveringtheHlocusrevealedthatanendogenousretrovirus(ERV)elementwasinserted intothefirstintronoftheKitgenewherethehoodedallelemaps.Asolitarylongterminalrepeat(LTR)wasfoundatthe samepositiontotheERVinsertioninanotheralleleoftheHlocus,whichcausesthesocalledIrish(hi)phenotype.TheERV andthesolitaryLTRinsertionswerecompletelyassociatedwiththehoodedandIrishcoatpatterns,respectively,acrossall coloredratstrainsexamined.Interestingly,all117albinoratstrainssharedtheERVinsertionwithoutanyexception,which stronglysuggeststhatthealbinomutationhadoriginallyoccurredinhoodedrats. Citation:KuramotoT,NakanishiS,OchiaiM,NakagamaH,VoigtB,etal.(2012)OriginsofAlbinoandHoodedRats:ImplicationsfromMolecularGeneticAnalysis acrossModernLaboratoryRatStrains.PLoSONE7(8):e43059.doi:10.1371/journal.pone.0043059 Editor:VincentLaudet,EcoleNormaleSupe′rieuredeLyon,Fran