Mutation at the Evi1 Locus in Junbo Mice Causes Susceptibility to Otitis Media 英文参考文献.docVIP

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Mutation at the Evi1 Locus in Junbo Mice Causes Susceptibility to Otitis Media 英文参考文献.doc

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Mutation at the Evi1 Locus in Junbo Mice Causes Susceptibility to Otitis Media 英文参考文献

MutationattheEvi1LocusinJunboMice CausesSusceptibilitytoOtitisMedia Nicholas Parkinson1[,Rachel E.Hardisty-Hughes1[,Hilda Tateossian1,Hsun-Tien Tsai1,2,Debra Brooker1,Sue Morse1, Zuzanna Lalane1,Francesca MacKenzie1,Martin Fray1,Pete Glenister1,Anne-Marie Woodward1,Sian Polley1, Ivana Barbaric1,Neil Dear3,Tertius A.Hough4,A.Jackie Hunter5,Michael T.Cheeseman1,4,Steve D.M. Brown1* 1 Mammalian Gentics Unit, Medical Research Council, Harwell, United Kingdom, 2DepartmentofOtorhinolaryngology,MacKayMemorialHospital,Taipei,Taiwan, 3Mammalian Genetics of Disease Group, School of Medicine, University of Sheffield, Sheffield, United Kingdom, 4 Mary Lyon Centre, Harwell, United Kingdom, 5 GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park, Harlow, United Kingdom Otitismedia(OM),inflammationofthemiddleear,remainsthemostcommoncauseofhearingimpairmentinchildren. Itisalsothemostcommoncauseofsurgeryinchildreninthedevelopedworld.Thereisevidencefromstudiesofthe humanpopulationandmousemodelsthatthereisasignificantgeneticcomponentpredisposingtoOM,yetnothingis known about the underlying genetic pathways involved in humans. We identified an N-ethyl-N-nitrosourea-induced dominant mouse mutant Junbo with hearing loss due to chronic suppurative OM and otorrhea. This develops from acuteOMthatarisesspontaneouslyinthepostnatalperiod,withtheageofonsetandearlyseveritydependentonthe microbiologicalstatusofthemiceandtheirairquality.Wehaveidentifiedthecausalmutation,amissensechangein theC-terminalzincfingerregionofthetranscriptionfactorEvi1.Thisproteinisexpressedinmiddleearbasalepithelial cells,fibroblasts,andneutrophilleukocytesatpostnatalday13and21wheninflammatorychangesareunderway.The identification and characterization of the Junbo mutant elaborates a novel role for Evi1 in mammalian disease and implicatesanewpathwayingeneticpredispositiontoOM. Citation:ParkinsonN,Hardisty-HughesRE,TateossianH,TsaiHT,BrookerD,etal.(2006)MutationattheEvi1locusinJunbomicecausessusceptibilityt