目的 建立心脏特异性表达KCNQ1V180L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KCNQ1V180L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 KCNQ1V180L转基因小鼠，PCR鉴定转基因小鼠的基因型，采用Western Blot鉴定KCNQ1V180L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KCNQ1V180L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 KCNQ1V180L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。
objective To generate the heart-specific KCNQ1V180L 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 KCNQ1V180L gene into the down stream of α-MHC promoter. The transgenic mice were created by the method of microinjection. 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 echocardiography and electrocardiography (ECG). Results Two lines of C57BL/6J transgenic mice with high levels of KCNQ1V180L expression were established. The heart of KCNQ1V180L transgenic mice showed thick ventricular wall, smaller ventricular chamber and increased fractionl shortening (FS%) compared with that of the non transgenic mice. Ventricular repolarization dysfunction was determined by ECG. Conclusions The KCNQ1V180L 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.
吕丹.心脏特异性表达KCNQ1V180L转基因小鼠的建立及表型分析[J].中国比较医学杂志,2012,(11).
复制