心脏特异性表达KCNQ1^（V180L）转基因小鼠的建立及表型分析

目的建立心脏特异性表达KCNQ1^V180 L转基因小鼠,为研究KCNQ1基因功能及其突变与心律失常性心脏疾病的关系提供工具动物。方法把KCNQ1^V180 L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 KCNQ1^V180 L转基因小鼠,PCR鉴定转基因小鼠的基因型,采用Western Blot鉴定KCNQ1^V180 L在心脏组织中的表达,记录转基因小鼠死亡情况,超声分析转基因小鼠心脏结构形态和功能改变,心电分析转基因小鼠心肌电生理变化。结果建立了2个心脏组织特异性表达KCNQ1^V180 L转基因小鼠品系。转基因小鼠离乳前即出现猝死;超声检查显示转基因小鼠左心室内径变短,心室壁变厚,短轴缩短率增加;心电分析显示其心室复极异常。结论 KCNQ1^V180 L转基因小鼠具有临床长QT综合征类似的病理改变,可作为研究KCNQ1基因功能及其突变与心律失常发病机制的疾病动物模型。

Establishment of Heart-specific KCNQ1Vl80L Transgenic Mice and Phenotype Analysis

Objective To generate the heart-specific KCNQ1vl80L expression transgenic mice and an animal model for the study of KCNQ1 function and its effects on arrhythmia. Methods The transgenic vector was constructed by inserting the human KCNQ1vl80L gene into the down stream of a-MHC promoter. The transgenic mice were created by the method of microinjeetion. The genotype of transgenic line was identified by PCR and the expression level of the gene was determined by Western Blot. The pathologic changes were analyzed with eehocardiography and electrocardiography （ECG）. Results Two lines of C57BL/6J transgenic mice with high levels of KCNQ1vl80L expression were established. The heart of KCNQlVl80L transgenie mice showed thick ventricular wall, smaller ventrieular chamber and increased fractionl shortening （FS%） compared with that of the non transgenic mice. Ventricular repolarization dysfunction was determined by ECG. Conclusions The KCNQ1vls~L transgenic mice showed a similar phenotype with human long QT syndrome （LQTS）. The transgenic mouse could be an useful animal model for the research of KCNQ1 gene function and the relationship between KCNQ1 mutation and arrhythmia.