smads基因在小鼠内耳听觉器官发育中的信号调控作用

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1、军医进修学院硕士学位论文SignalTransductionMechanismofSmadsIntheDevelopmentofMouseEnbronicCochlearHearinglosshasaveryhighprevalence．Remarkableprogresshasbeenmadeinthecloningofdeafnessgenes．Thesefindingsofferthepromisetosignificantlyexpandourknowledgeonthemolecularmechanismsunderl

2、yingtheauditoryandvestibularfunctionsandOilthepathophysiologicalmechanismsforhearingloss．Butsometimesitisdifficulttoidentifythesegenesbecauseoflackclinicalcharacteristics，geneticheterogeneityandsmallfamilyconstellation．Inaddition，somerelatedgenesaredifficulttodiscove

3、rbecausethereisriosuitablerarelyconstellationwhichCanbeusedforlinkageanalysis．Theinnere雒structure，developmentandpathologyofauditorysensationshiftofmou．．qearcextremelysimilarwithhumanbeing．Thus，thestudyofmousedeafnessrelatedgenesofferanothermethodtoidentifypossibleman

4、kinddcaflocus．Smad4andSmad5a尬signaltransduetionmemberofU'ansforminggrowthfactor-IBsuperfamily，andmainlymediateBMP4signaltransduction．TGF-Bsuperfamilymembersparticipateregulatingtheblastodermaldevelopment，organicformation,epithefialfissularaccrementition,extracellular

5、metricalsynthesis,immlme舰etionandotherbiologicalproc鹤s．IthasbeenreportedthatBMPfamilymembersandtheirsignaltransductionmoleculeexpIessintheinnere封ofchicken,mouse,zebrafish,Xenopus．OurpreviousdatashowthatSmad4、Smad5geneknock-outc∞resultinmouseserioushearinglossandthein

6、nerearhearingorg{mincludingofhair∞lb．suppo．h培cells，sphalgangliondamaged．SoSmad4、Smad5genesprobablyare越

7、ditoIyfunctioncorrelationgenes．Butwhere,whenandhowtheyplayroleshasnotbeenreported．Th口霉fb托．thisstudyIlscfrozensectio璐andHEstainingtoobservethemorphologicalchangeofmo

8、usecochleaandimmunohistochcmistrytodetermine5军医进修学院硕士学位论文theexpressionofBMP4andSmad4，Smad5proteinsinthedevelopmentofmousecochlea,andtoinvestigatethesignaltransductionmechanismintheinner哪development．partone"thedevelopmentofmousecochleaobjeetive：Toexplorethedevelopment

9、alpI．0ccssofmouseinner哪andofferachoiceforselectsuitablemousemodelinstudyinginnereardevelopment．Methods：Theinnercarswcreobtainedfrom