Phenotyping cardiomyopathy in adult zebrafish

Abstract

Hypertrophic cardiomyopathy (HCM) is usually manifested by increased myofilament Ca sensitivity, excessive contractility, and impaired relaxation. In contrast, dilated cardiomyopathy (DCM) originates from insufficient sarcomere contractility and reduced cardiac pump function, subsequently resulting in heart failure. The zebrafish has emerged as a new model of human cardiomyopathy with high-throughput screening, which will facilitate the discovery of novel genetic factors and the development of new therapies. Given the small hearts of zebrafish, better phenotyping tools are needed to discern different types of cardiomyopathy, such as HCM and DCM. This article reviews the existing models of cardiomyopathy, available morphologic and functional methods, and current understanding of the different types of cardiomyopathy in adult zebrafish.

Deletion of Gtpbp3 in zebrafish revealed the hypertrophic cardiomyopathy manifested by aberrant mitochondrial tRNA metabolism

“…Furthermore, gtpbp3 −/− adult zebrafish displayed the hypertrophy of cardiac myocytes and myocardial fiber disarray in ventricles. These cardiac defects in gtpbp3 −/- zebrafish recapitulated the clinical phenotypes in HCM patients carrying the GTPBP3 mutations (32,91–93). These data demonstrated that the gtpbp3 -deletion-induced mitochondrial dysfunctions caused hypertrophic cardiomyopathy.…”

Animal Models of Cardiomyopathies

“…The zebra fish (Danio rerio) model remains one of the most effective technologies for discovering and functional studying novel cardiomyopathy candidate genes, especially the ability to use morpholino knockdown techniques in fish models [26,41,42]. Compared with other vertebrate models, the zebra fish embryos are transparent allowing genetic engineering approaches to apply fluorescent reporter transgenes with genetic fate mapping strategies combined with high-resolution, high-throughput microscopy imaging in vivo of the heart [43,44].…”

Modeling Inherited Cardiomyopathies in Adult Zebrafish for Precision Medicine

“…Because a zebrafish heart is only sized about 1-2 mm in diameter, novel phenotyping toolkits, such as high-frequency echocardiography, the Langendorff ex vivo system, ECG, and single-myofibril contractility analysis, have been developed to define progression of cardiac remodeling in zebrafish (Dvornikov et al, 2014;Lin et al, 2015;Koth et al, 2017;Merrifield et al, 2017;Wang et al, 2017;Stoyek et al, 2018;Zhang et al, 2018;Wakamatsu et al, 2019;Yan et al, 2020). Because these toolkits have already been comprehensively reviewed recently (Dvornikov et al, 2018;Lin et al, 2020), we only list some new techniques in Table 2. Partially because these new technologies are not readily accessible, many published adult zebrafish inherited cardiomyopathy models have not been sufficiently phenotyped to be categorized into a certain type of cardiomyopathy.…”