cTnT^(R92Q)转基因小鼠肥厚型心肌病模型的建立  

The Establishment of the cTnT^(R92Q) Transgenic Mouse Model of Hypertrophic Cardiomyopathy

作　　者：董伟[1] 冯娟[1] 全雄志[1] 陈炜[1] 祝梅香[1] 刘亚莉[1] 张连峰[1] 

机构地区：[1]中国医学科学院实验动物研究所卫生部人类疾病比较医学重点实验室,北京100021

出　　处：《中国比较医学杂志》2008年第5期5-8,I0002,共5页Chinese Journal of Comparative Medicine

基　　金：北京市转基因平台建设项目TC2006-02(Z0006303041231);中央级公益性科研院所基本科研业务费专项基金(DWS200704)

摘　　要：目的建立cTnTR92Q肥厚型心肌病的转基因小鼠模型。方法把cTnTR92Q基因插入-αMHC启动子下游,构建转基因表达载体,通过显微注射法建立cTnTR92Q转基因C57BL/6J小鼠。PCR鉴定cTnTR92Q转基因小鼠的基因表型,RT-PCR检测基因表达,光学显微镜和超声检测cTnTR92Q转基因小鼠心脏的病理改变。结果建立了3个不同表达水平的cTnTR92Q转基因小鼠品系。转入的cTnTR92Q基因在心脏组织的表达水平高于内源性cTnT。组织学分析显示cTnTR92Q转基因小鼠心脏变大,心室壁肥厚,心腔变小,心肌细胞排列紊乱,心肌间质纤维增多。超声检查显示心室壁变厚,收缩期容积和舒张期容积显著缩小,射血分数、短轴缩短率明显增加。结论cTnTR92Q转基因小鼠心脏变大,室壁变厚,心腔变小,心肌细胞排列紊乱,间质纤维化以及心肌舒张功能失调,说明成功建立了cTnTR92Q转基因小鼠肥厚型心肌病模型,为研究肥厚型心肌病发病机制和药物研发提供了有价值的动物模型。Objective To establish the transgenic mouse of cTnT^R92Q gene to make an animal model of hypertrophic cardiomyopathy （HCM）. Methods The transgenic plasmid was constructed by inserting the cTnT^R92Q gene in the downstream of α-MHC promoter. The transgenic mice were produced by micreinjection method and the genotype was detected by PCR. The expression level of the gene was determined with RT-PCR. The pathologic changes were observed under microscope and analyzed with echocardiography. Results Three lines of transgenic C57BL/6J mouse of cTnT^R92Q gene with different expression levels were established. The expression of the cTnT^R92Q gene was obviously detected in the heart tissues. The heart of cTnT^R92Q transgenic mouse showed hypertrophic ventricular wall, reduced ventricular chamber, myocyte disarray, and interstitial fibrosis compared with that of the wild type. The Ejection fraction （EF%） and Fractional shortening （FS%） were increased obviously. Conclusions The expression of mutant cTnT^R92Q gene in heart caused ventricular chamber reducing, myocardial hypertrophy, myocyte disarray, interstitial fibrosis, and diastolic dysfunction, which suggest that the cTnT^R92Q gene transgenic mouse is an useful animal model of HCM.

关 键 词：心肌肌钙蛋白T 肥厚型心肌病 转基因模型 基因突变 

分 类 号：R541[医药卫生—心血管疾病]