Roles of the Espin Actin-Bundling Proteins in the Morphogenesis and Stabilization of Hair Cell Stereocilia Revealed in CBACaJ Congenic Jerker Mice 英文参考文献.docVIP

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Roles of the Espin Actin-Bundling Proteins in the Morphogenesis and Stabilization of Hair Cell Stereocilia Revealed in CBACaJ Congenic Jerker Mice 英文参考文献.doc

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Roles of the Espin Actin-Bundling Proteins in the Morphogenesis and Stabilization of Hair Cell Stereocilia Revealed in CBACaJ Congenic Jerker Mice 英文参考文献

RolesoftheEspinActin-BundlingProteinsinthe MorphogenesisandStabilizationofHairCellStereocilia RevealedinCBA/CaJCongenicJerkerMice GabriellaSekerkova′1,Claus-PeterRichter2,3,JamesR.Bartles1,3 * 1Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America, 2Department of Otolaryngology,NorthwesternUniversityFeinbergSchoolofMedicine,Chicago,Illinois,UnitedStatesofAmerica,3HughKnowlesCenterforClinicalandBasicSciencein HearingandItsDisorders,NorthwesternUniversityFeinbergSchoolofMedicine,Chicago,Illinois,UnitedStatesofAmerica Abstract Hearingandvestibularfunctiondependonmechanosensorystaircasecollectionsofhaircellstereocilia,whichareproduced frommicrovillus-likeprecursorsastheirparallelactinbundlescaffoldsincreaseindiameterandelongateorshorten.Haircell stereocilia contain multiple classes of actin-bundling protein, but little is known about what each class contributes. To investigate the roles of the espin class of actin-bundling protein, we used a genetic approach that benefited from a judicious selection of mouse background strain and an examination of the effects of heterozygosity. A congenic jerker mouselinewaspreparedbyrepeatedbackcrossingintotheinbredCBA/CaJstrain,whichisknownforexcellenthearingand minimalage-relatedhearingloss.Wecomparedstereociliainwild-typeCBA/CaJmice,jerkerhomozygotesthatlackespin proteinsowingtoaframeshiftmutationintheespingene,andjerkerheterozygotesthatcontainreducedespinlevels.The lackofespinsradicallyimpairedstereociliarymorphogenesis,resultinginstereociliathatwereabnormallythinandshort, with reduced differential elongation to form a staircase. Mean stereociliary diameter did not increase beyond ,0.10– 0.14mm,makingstereocilia,30%–60%thinnerthanwildtypeandsuggestingthattheycontained,50%–85%feweractin filaments.Thesecharacteristicsindicatearequirementforespinsintheappositionalgrowthanddifferentialelongationof thestereociliaryparallelactinbundleandfittheknownbiol