PDF(Pubmed)
Abstract：
Congenital heart defects (CHDs) are common human birth defects. Genetic mutations potentially cause the exhibition of various pathological phenotypes associated with CHDs, occurring alone or as part of certain syndromes. Zebrafish, a model organism with a strong molecular conservation similar to humans, is commonly used in studies on cardiovascular diseases owing to its advantageous features, such as a similarity to human electrophysiology, transparent embryos and larvae for observation, and suitability for forward and reverse genetics technology, to create various economical and easily controlled zebrafish CHD models. In this review, we outline the pros and cons of zebrafish CHD models created by genetic mutations associated with single defects and syndromes and the underlying pathogenic mechanism of CHDs discovered in these models. The challenges of zebrafish CHD models generated through gene editing are also discussed, since the cardiac phenotypes resulting from a single-candidate pathological gene mutation in zebrafish might not mirror the corresponding human phenotypes. The comprehensive review of these zebrafish CHD models will facilitate the understanding of the pathogenic mechanisms of CHDs and offer new opportunities for their treatments and intervention strategies.
摘要：
先天性心脏病（CHDs）是人类常见的出生缺陷。基因突变可能导致与CHD相关的各种病理表型的表现，单独发生或作为某些综合征的一部分。斑马鱼,具有与人类相似的强分子保守性的模型生物，由于其优点，通常用于心血管疾病的研究，比如与人体电生理学的相似性，观察透明的胚胎和幼虫，以及正向和反向遗传学技术的适用性，创造各种经济和易于控制的斑马鱼CHD模型。在这次审查中,我们概述了斑马鱼CHD模型的利弊,这些模型是由与单一缺陷和综合征相关的基因突变创建的,以及在这些模型中发现的CHD的潜在致病机制.还讨论了通过基因编辑产生的斑马鱼CHD模型的挑战，因为斑马鱼中单个候选病理基因突变导致的心脏表型可能不反映相应的人类表型。对这些斑马鱼CHD模型的全面回顾将有助于理解CHD的致病机制，并为其治疗和干预策略提供新的机会。
