The Biomedical Sciences Institute of Qingdao University (Qingdao Branch of SJTU Bio-X Institutes), Qingdao University, Qingdao 266021, China.
School of Public Health, Qingdao University, Qingdao 266021, China.
Int J Mol Sci. 2023 Feb 18;24(4):4106. doi: 10.3390/ijms24044106.
Arrhythmogenic cardiomyopathy (ACM) is largely an autosomal dominant genetic disorder manifesting fibrofatty infiltration and ventricular arrhythmia with predominantly right ventricular involvement. ACM is one of the major conditions associated with an increased risk of sudden cardiac death, most notably in young individuals and athletes. ACM has strong genetic determinants, and genetic variants in more than 25 genes have been identified to be associated with ACM, accounting for approximately 60% of ACM cases. Genetic studies of ACM in vertebrate animal models such as zebrafish (), which are highly amenable to large-scale genetic and drug screenings, offer unique opportunities to identify and functionally assess new genetic variants associated with ACM and to dissect the underlying molecular and cellular mechanisms at the whole-organism level. Here, we summarize key genes implicated in ACM. We discuss the use of zebrafish models, categorized according to gene manipulation approaches, such as gene knockdown, gene knock-out, transgenic overexpression, and CRISPR/Cas9-mediated knock-in, to study the genetic underpinning and mechanism of ACM. Information gained from genetic and pharmacogenomic studies in such animal models can not only increase our understanding of the pathophysiology of disease progression, but also guide disease diagnosis, prognosis, and the development of innovative therapeutic strategies.
致心律失常性右室心肌病（arrhythmogenic right ventricular cardiomyopathy，ACM）主要是一种常染色体显性遗传疾病，表现为纤维脂肪浸润和室性心律失常，主要累及右心室。ACM 是与心脏性猝死风险增加相关的主要疾病之一，尤其是在年轻人和运动员中。ACM 具有很强的遗传决定因素，已有 25 多种基因的变异被确定与 ACM 相关，约占 ACM 病例的 60%。在斑马鱼等脊椎动物模型中对 ACM 的遗传研究（），非常适合进行大规模的遗传和药物筛选，为鉴定和功能评估与 ACM 相关的新遗传变异体，并在整体水平上剖析潜在的分子和细胞机制提供了独特的机会。在此，我们总结了与 ACM 相关的关键基因。我们讨论了根据基因操作方法（如基因敲低、基因敲除、转基因过表达和 CRISPR/Cas9 介导的基因敲入）对斑马鱼模型的使用，以研究 ACM 的遗传基础和机制。从这些动物模型中的遗传和药物基因组学研究中获得的信息不仅可以增加我们对疾病进展病理生理学的理解，还可以指导疾病诊断、预后和创新治疗策略的制定。
