Turan Sifa, Chaillet J Richard, Stapleton Margaret C, Wu Yijen L
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
Magee-Womens Research Institute, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Adv Exp Med Biol. 2023;1396:53-73. doi: 10.1007/978-981-19-5642-3_4.
Congenital heart disease (CHD) has a strong genetic etiology, making it a likely candidate for therapeutic intervention using genetic editing. Complex genetics involving an orchestrated series of genetic events and over 400 genes are responsible for myocardial development. Cooperation is required from a vast series of genetic networks, and mutations in such can lead to CHD and cardiovascular abnormalities, affecting up to 1% of all live births. Genome editing technologies are becoming better studied and with time and improved logistics, CHD could be a prime therapeutic target. Syndromic, nonsyndromic, and cases of familial inheritance all involve identifiable causative mutations and thus have the potential for genome editing therapy. Mouse models are well-suited to study and predict clinical outcome. This review summarizes the anatomical and genetic timeline of myocardial development in both mice and humans, the potential of gene editing in typical CHD categories, as well as the use of mice thus far in reproducing models of human CHD and correcting the mutations that create them.
先天性心脏病（CHD）具有很强的遗传病因，这使其成为使用基因编辑进行治疗干预的可能候选对象。涉及一系列精心编排的遗传事件和400多个基因的复杂遗传学负责心肌发育。大量的遗传网络需要协同作用，其中的突变可导致CHD和心血管异常，影响所有活产婴儿的1%。随着时间的推移以及后勤保障的改善，基因编辑技术得到了更好的研究，CHD可能成为主要的治疗靶点。综合征性、非综合征性以及家族遗传性病例均涉及可识别的致病突变，因此具有进行基因编辑治疗的潜力。小鼠模型非常适合研究和预测临床结果。本综述总结了小鼠和人类心肌发育的解剖学和遗传学时间线、典型CHD类别中基因编辑的潜力，以及迄今为止使用小鼠复制人类CHD模型并纠正导致这些模型的突变的情况。
