低密度脂蛋白受体相关蛋白2结合蛋白在心脏特异转基因小鼠中引起的心脏功能代偿

目的建立心脏特异表达的低密度脂蛋白受体相关蛋白2结合蛋白(Lrp2bp)转基因小鼠,研究该基因在心肌病发病中的作用。方法克隆鼠源Lrp2bp基因入α-MHC启动子下游,构建a-MHC-Lrp2bp表达载体,显微注射法建立Lrp2bp转基因小鼠。PCR鉴定转基因首建鼠的基因型。Westernblotting鉴定Lrp2bp在心脏中的表达,心脏超声检测转基因鼠及野生型小鼠心脏结构和功能,透射电镜观察心肌细胞的超微结构改变。结果得到了4个Lrp2bp转基因品系,其中3个品系心脏Lrp2bp蛋白表达量与同龄野生型鼠相比明显增加。1M龄转基因小鼠与同窝阴性对照小鼠相比,心壁变厚,心腔变大,射血分数和短轴缩短率下降。结论心脏特异表达的Lrp2bp基因能引起心肌肥厚表型,可能是参与心肌代偿性肥厚的基因之一。

Compensation Effect of Lrp2bp on the Heart Function in the Heart Tissue Specific Transgenic Mice

Objective To generate heart tissue specific Lrp2bp transgenic mouse and to study its effects on cardiomyopathy.Methods The transgenic plasmid was constructed by inserting the murine Lrp2bp gene into the downstream of α-MHC promoter.The transgenic mice were created by microinjection.The genotype of transgenic line was identified by PCR and the expression level of the gene was determined by Western blotting.The cardiac function and geometry were detected by echocardiography.The ultrastructural changes of cardiomyocytes from Lrp2bp transgenic mice were observed by transmission electron microscopy.Results Three lines of C57BL /6J transgenic mice with high level of Lrp2bp expression were identified from four transgenic founders.At 1 month old,the Lrp2bp transgenic mice showed increased thickness of the ventricular wall,dilated ventricular chamber,decreased ejection fraction and decreased fractional shortening compared with that of wild type mice.Conclusion Transgenic mice with cardiac tissue specific Lrp2bp gene have been established successfully and Lrp2bp caused compensation effect on the cardiomyopathy in the transgenic mice.