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目的建立心脏特异表达的cTnIR145G转基因小鼠,同时初步分析其心脏功能及形态变化。方法把cTnIR145G基因插入α-MHC启动子下游,构建转基因表达载体,显微注射法建立C57BL/6J cTnIR145G转基因小鼠,PCR鉴定转基因小鼠的基因型,采用Western Blot鉴定cTnIR145G在心脏组织中的表达,记录转基因小鼠死亡情况,超声检测,心电分析及组织学观察转基因小鼠心脏的病理改变。结果建立了4个表达水平不同的心脏组织特异表达的cTnIR145G转基因小鼠品系。高表达小鼠品系在成熟前即出现猝死;超声检查显示小鼠左心室内径及容积显著减小,室壁增厚,短轴缩短率显著增加;心电分析显示其心室复极缺陷,组织学染色发现小鼠心肌细胞排列出现紊乱,心肌细胞不均匀肥大。结论 cTnIR145G转基因小鼠具有与肥厚型心肌病类似的病理变化,为cTnI突变与心肌病发病机制的关系的研究提供了有价值的疾病动物模型。
Objective To establish cardiac-specific cTnIR145G transgenic mice, and analyze its cardiac function and morphological changes. Methods The cTnIR145G gene was inserted into the downstream of α-MHC promoter to construct transgenic expression vector. The C57BL / 6J cTnIR145G transgenic mice were established by microinjection. The genotypes of transgenic mice were identified by PCR. The expression of cTnIR145G in heart tissues was identified by Western Blot The death of transgenic mice was recorded. Ultrasound, electrocardiogram and histology were used to observe the pathological changes in the heart of transgenic mice. Results Four cTnIR145G transgenic mice with different expression levels of cardiac tissue were established. Sudden death was observed in the high-expression mouse strain before maturation. Ultrasonography showed that the left ventricular diameter and volume were significantly reduced, the ventricular wall thickening and short axis shortening were significantly increased, and ECG analysis showed ventricular repolarization defect and histology Staining found that the arrangement of myocardial cells appear disorder, uneven myocardial hypertrophy. Conclusions cTnIR145G transgenic mice have similar pathological changes as hypertrophic cardiomyopathy and provide valuable animal models of disease for the study of the relationship between cTnI mutation and the pathogenesis of cardiomyopathy.