先天性心脏病相关基因线粒体内膜稳定蛋白41（TAMM41）在模式生物斑马鱼胚胎心脏发育过程中生物学作用的研究

先天性心脏病后果严重，病因多变。越来越多的证据表明，线粒体异常在该病中起重要作用。人类3p- 缺失综合征经常伴有先天性心脏发育异常，线粒体内膜稳定蛋白TAMM41定位于缺失片段内，很可能与心脏发育直接相关。我们对散发的118例伴有房室瓣膜缺损的先心病患儿进行了3号染色体短臂先心病易感区段的测序，发现在3例患儿中存在TAMM41基因的杂合子点突变。本课题将采用利用反义寡核苷酸链（morpholino，MO）介导的knockdown技术以及CRISP9介导的基因knockout技术，siRNA干扰技术等深入研究TAMM41对线粒体形态、功能、以及对心肌细胞增殖以及再生的影响。这将为了解相关疾病的发生机制并为寻找新的疾病预防及治疗策略提供依据。

Congenital heart disease (CHD) often leads to heart failure and death, the etiology of CHD is varied. Emerging evidences indicate that mitochondrial dysfunction accounts for this disease. TAMM41, a highly conserved mitochondrial membrane maintenance protein, is involved in human 3p- syndrome related CHD. Through screening of the CHD sensitive region of 3p25 deletion syndrome among 118 sporadic atrioventricular septal defect (AVSD) patients, we identified three AVSD cases carrying heterozygous intronic mutations of TAMM41. . Here we will use model organism zebrafish in combination with a variety of experimental methods such as MO-mediated gene knockdown technology，CRISPR/Cas9 mediated gene knockout technology，siRNA to study the role of TAMM41 in heart development. Hopefully this work may help us to find the potential cause of CHD and relevant drug target, thus to improve the genetic counseling and disease intervention.