Evaluation of Pax6 Mutant Rat as a Model for Autism 英文参考文献.docVIP

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Evaluation of Pax6 Mutant Rat as a Model for Autism 英文参考文献.doc

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Evaluation of Pax6 Mutant Rat as a Model for Autism 英文参考文献

EvaluationofPax6MutantRatasaModelforAutism ToshikoUmeda1.,NorikoTakashima2,3.,RyokoNakagawa4,MotokoMaekawa5,ShiroIkegami3,6 ,Takeo Yoshikawa5,KazutoKobayashi7,KazuoOkanoya4,KaoruInokuchi3,8,NorikoOsumi1* 1Division ofDevelopmental Neuroscience,Tohoku University Graduate School of Medicine, Sendai, Japan, 2Laboratory for Behavioral and Developmental Disorders, RIKEN Brain Science Institute, Wako, Japan, 3Mitsubishi Kagaku Institute of Life Sciences (MITILS), Tokyo, Japan, 4Laboratory for Biolinguistics, RIKEN Brain Science Institute,Wako,Japan,5LaboratoryforMolecularPsychiatry,RIKENBrainScienceInstitute,Wako,Japan,6DepartmentofPsychology,SaitamaInstituteofTechnology, Fukaya,Japan,7DepartmentofMolecularGenetics,InstituteofBiomedicalSciences,FukushimaMedicalUniversitySchoolofMedicine,Fukushima,Japan,8Department ofBiochemistry,FacultyofMedicine,GraduateSchoolofMedicineandPharmaceuticalSciences,UniversityofToyama,Toyama,Japan Abstract Autismisahighlyvariablebraindevelopmentaldisorderandhasastronggeneticbasis.Pax6isapivotalplayerinbrain developmentandmaintenance.Itisexpressedinembryonicandadultneuralstemcells,inastrocytesintheentirecentral nervoussystem,andinneuronsintheolfactorybulb,amygdala,thalamus,andcerebellum,functioninginhighlycontext- 2+ dependentmanners.WehaverecentlyreportedthatPax6heterozygousmutant(rSey / )ratswithaspontaneousmutation 2+ inthePax6gene,showimpairedprepulseinhibition(PPI).Inthepresentstudy,wefurtherexaminedbehaviorsofrSey / rats and revealed that they exhibited abnormality in social interaction (more aggression and withdrawal) in addition to impairmentinrearingactivityandinfear-conditionedmemory.Ultrasonicvocalization(USV)inrSey2+ratpupswasnormal in male but abnormal in female. Moreover, treatment with clozapine successfully recovered the defects in sensorimotor gatingfunction,butnotinfear-conditionedmemory.Takentogetherwithourpriorhumangeneticdataandresultsinother 2+ratslikelyhavesomephenotypiccomponentsofautism. literatures,rSey