Meox1在心脏过表达引起转基因小鼠扩张性心肌病

目的建立心脏特异表达Meox1转基因小鼠,研究Meox1对心脏发育及心肌病的调节作用。方法利用心脏特异启动子α-MHC构建转基因表达载体,显微注射法建立Meox1转基因小鼠,PCR鉴定转基因小鼠的基因型,Western blot检测Meox1在心脏组织中的表达,心脏超声检测转基因小鼠及野生小鼠的心脏结构和功能。结果在生理状态下,Meox1基因只在幼鼠心脏中表达,在病理状态下,Meox1基因在成年心肌病小鼠的心脏组织表达升高。通过显微注射,建立了两个Meox1基因在心脏组织的表达水平明显高于同龄对照小鼠的转基因小鼠品系。与野生型小鼠相比,两个Meox1转基因小鼠品系收缩期左室内径分别增加7.2%、12.8%（P〈0.01,n=16）,舒张期左室内径分别增加15.6%、24.2%（P〈0.01,n=16）,收缩期容积分别增加36.8%、65.7%（P〈0.01,n=16）,舒张期容积分别增加18.2%、33.8%（P〈0.01,n=16）。射血分数分别减小6.6%、9.3%（P〈0.05,n=16）,短轴内径缩短率分别减小9.4%、12.3%（P〈0.05,n=16）。结论Meox1在心肌病心脏中表达,其在心脏高表达引起心脏左室内径增加,收缩期容积和舒张期容积显著增大,射血分数及短轴缩短率减少等扩张性心肌病表型,是参与心肌病病理发生的基因之一。

Over-Expression of Meox1 in Heart Tissue Causes Dilated Cardiomyopathy in the Transgenic Mouse

Objective To establish heart-specific Meox1 expression transgenic mice and to investigate its regulatory effect on the development of heart and cardiomyopathy.Methods The transgenic plasmid was constructed by inserting the mouse Meox1 gene into the down-stream of α-MHC promoter.The transgenic mice were generated by microinjection.The genotype of transgenic lines was identified by PCR,and the expression levels of the Meox1 gene were detected by Western blot.The pathologic and functional changes of the heart were analyzed by echocardiography.Results The results of Western blot showed that the expression of Meox1 was only detected in the heart of one-week old wide-type mice,but its expression was up-regulated in the adult mice with hypertrophic cardiomyopathy（HCM）.The heartspecific transgenic C57BL /6J mice were established and used to analyze its effect on heart by echocardiography.Compared with the wild type mice,both of the two lines of Meox1 transgenic mice showed significantly heart remodeling with increased left ventricular systolic diameter（7.2% or 12.8%,P 0.01,n=16）,increased left ventricular diastolic diameter（15.6% or 24.2% ,P 0.01,n=16） ,increased systolic volume（36.8% or 65.7% ,P 0.01,n=16）,and increased diastolic volume（18.2% ,33.8% ,P 0.01,n=16）.Compared with the wild type mice,both of the two lines of Meox1 transgenic mice showed weaker heart function with decreased ejection fraction（6.6% or 9.3% ,P 0.05,n=16）,and decreased fraction shortening（9.4% ,or 12.3% ,P 0.05,n=16）.Conclusions The Meox1 is expressed during the pathogenesis of cardiomyopathy.Over-expression of Meox1 in the heart of the transgenic mice causes dilated cardiomyopathy.It suggests that Meox1 may be one of modifier genes which enhances pathogenesis of cardiomyopathy.