State Key Laboratory of Developmental Biology of Freshwater Fish, Key Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, College of Physical Education, Hunan Normal University, Changsha 410000, China.
Int J Mol Sci. 2024 May 29;25(11):5943. doi: 10.3390/ijms25115943.
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.
先天性心脏病（CHD）是常见的人类出生缺陷。基因突变可能导致与 CHD 相关的各种病理表型的表现，这些表型单独出现或作为某些综合征的一部分出现。斑马鱼作为一种与人类具有很强分子保守性的模式生物，由于其具有类似于人类电生理学、透明胚胎和幼虫便于观察、适合正向和反向遗传学技术等优势，常用于心血管疾病的研究，可创建各种经济且易于控制的斑马鱼 CHD 模型。在这篇综述中，我们概述了由单缺陷和综合征相关基因突变以及在这些模型中发现的 CHD 潜在发病机制所创建的斑马鱼 CHD 模型的优缺点。我们还讨论了通过基因编辑生成的斑马鱼 CHD 模型所面临的挑战，因为在斑马鱼中单一致病基因突变产生的心脏表型可能无法反映相应的人类表型。对这些斑马鱼 CHD 模型的全面综述将有助于理解 CHD 的发病机制，并为其治疗和干预策略提供新的机会。
