简介:FragileXsyndromeisthemostcommonformofinheritedmentalretardationaffectingupto1in4000individuals.ThesyndromeisinducedbyamutationintheFMR1gene,causingadeficiencyinitsgeneby-productFMRP.ImpairmentinthenormalfunctioningofFMRPleadstolearningandmemorydeficitsandheightenedsensitivitytosensorystimuli,includingsound(hyperacusis).ThemolecularbasisoffragileXsyndromeisthoroughlyunderstood;however,theneuralmechanismsunderlyinghyperacusishavenotyetbeendetermined.Astheinferiorcolliculus(IC)istheprincipalmidbrainnucleusoftheauditorypathway,thecurrentstudyaddressesthequestionsunderlyingtheneuralmechanismofhyperacusiswithintheICoffragileXmice.AcuteexperimentswereperformedinwhichelectrophysiologicalrecordingsoftheICinFMR1-KOandWTmiceweremeasured.ResultsshowedthatQ-valuesforWTweresignificantlylargerthanthatofFMR-1KOmice,indicatingthatWTmiceexhibitsharpertuningcurvesthanFMR1-KOmice.WealsofoundtheratioofthemonotonicneuronsintheKOmicewasmuchhigherthantheWTmice.TheseresultssuggestthatlackofFMRPintheauditorysystemaffectsthedevelopmentalmaturationandfunctionofstructureswithintheauditorypathway,andinthiscasespecificallytheIC.ThedysfunctionobservedwithintheauditoryneuralpathwayandinparticulartheICmayberelatedtotheincreasedsusceptibilitytosoundasseeninindividualswithfragileXsyndrome.OurstudymayhelponunderstandingthemechanismsofthefragileXsyndromeandhyperacusis.
简介:目的探索Math1基因导人大鼠前庭简便有效的方法和途径,为前庭功能障碍基因治疗的相关研究提供参考。方法将20只成年Wistar大鼠分为缺失E1、E3基因片段且构建有Math1基因和增强型绿色荧光蛋白报告基凶的复制缺陷型腺病毒(adnovirus—Math1—enhancedgreenfluorescenceprotein,Ad—Math1—EGFP)鼓阶导入组和前庭阶导人组.Ad—Math1—EGFP导入组大鼠在右耳通过耳蜗底转鼓阶或前庭阶打孔的方法导人物理滴度为2.1×1011v.p/ml的上述腺病毒5μl。在导入3天、7天后分别将动物处死,进行GFP表达观察。结果导入Ad—Mathl—EGFP3天后,前庭阶导入组大鼠的前庭终末器官及耳蜗均出现明显的GFP阳性表达;而鼓阶导入组的表达则局限于耳蜗,7天后仍未见前庭终末器官的GFP阳性表达。结论耳蜗底转前庭阶打孔可以作为Math1基因导入大鼠前庭简便有效的途径。
简介:目的:寻找并确定一个中国常染色体隐性遗传性聋小家系的遗传分子病因,探讨该突变在中国人群中的携带情况。方法采集一个常染色体隐性遗传性耳聋小家系(No.1953)样本4例、常染色体隐性遗传性聋患者样本50例、正常听力对照样本208例,临床资料完整;对No.1953家系先证者样本进行全外显子组测序及生物信息学分析,确定可疑致病突变后采用突变位点PCR扩增、Sanger测序在该家系内部、隐性耳聋样本及正常听力样本中进行验证。结果TMC1基因复合杂合突变c.589G>A和c.1171C>T是No.1953家系的致聋突变;本组隐性耳聋患者及正常人均未发现携带该变异。结论TMC1基因复合杂合突变c.589G>A和c.1171C>T为常染色体隐性遗传性耳聋家系No.1953的致聋突变,在中国人群中的携带率低,该突变的确定丰富了遗传性聋的突变谱。
简介:ObjectiveAlongwithchangesintheecologysystemandundertheinfluenceofvariousenvironmentalfactors,theincidenceoftumorhasbeenincreasingyearafteryear.Thereisatrendincancertherapytomovetocombinedtherapiesinvolvingsurgery,radiationchemotherapyandgenetherapy.Cancergenetherapyinrecentyearshasbroughtnewopportunitiesfortreatmentoftumor.Itsadvantagesincludelowrateoftolerance,insensitivitytocellcycles,highspecificityandcoverageforbothprimaryandmetastatictumors1,2.However,thisisanewfieldofclinicalresearch.RegardingthecorrelationamongtheSTAT3,CyclinD1andP21genesandtumors,researchhasfocusedontheirexpressionandregulation.Thisarticleprovidesasummaryofrelatedresearch.