摘要
目的建立心脏特异表达Dkk3转基因模型小鼠,研究Dkk3对心脏发育及和心肌病的调节作用。方法把Dkk3基因插入心肌特异启动子-αMHC下游,构建转基因表达载体,显微注射法建立C57BL/6J Dkk3转基因小鼠,PCR鉴定转基因小鼠基因型,采用Northern blot检测Dkk3在心脏组织中的表达,HE染色和超声检查转基因小鼠心脏结构和功能。结果建立了3个不同表达水平的Dkk3转基因小鼠品系。转入的Dkk3基因在心脏组织的表达水平均高于同龄对照小鼠。组织学分析显示Dkk3小鼠室壁变厚,心腔减小,心肌细胞排列轻度紊乱。超声检查显示心室壁变厚,收缩期容积和舒张期容积显著减小,射血分数,短轴缩短率增加。结论Dkk3过表达导致转基因小鼠室壁变厚,心腔减小,心肌细胞排列轻度紊乱,心肌舒张功能轻度失调。
Objective To generate the heart-specific expression Dkk3 transgenic mice and to make an anima model for the study of its function and effects on cardiomyopathy. Methods The transgenic vector was constructed by inserting the murine Dkk3 gene into the down stream of α-MHC promoter. The transgenie 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 Northern blot. The pathologic changes were observed by microscopy and analyzed with echocardiography. Results Three lines of C57BL/6J transgenic mice with high level of Dkk3 were establisment. The heart of Dkk3 transgenic mice showed hypertrophic ventrieular wall, reduced ventrieular chamber, myocyte disarray compared with that of wild type. The Ejection fraction (EF%) and Fraetionl shortening (FS%) were increased. Conclusions The expression of Dkk3 gene in heart caused ventricular chamber reducing, myocardial hypertrophy, myocyte disarray and diastolic dysfunction.
出处
《中国比较医学杂志》
CAS
2009年第5期16-19,I0005,I0006,共6页
Chinese Journal of Comparative Medicine
基金
卫生部项目(编号200802036)