Modeling Inherited Cardiomyopathies in Adult Zebrafish for Precision Medicine

Abstract

Cardiomyopathies are a highly heterogeneous group of heart muscle disorders. More than 100 causative genes have been linked to various cardiomyopathies, which explain about half of familial cardiomyopathy cases. More than a dozen candidate therapeutic signaling pathways have been identified; however, precision medicine is not being used to treat the various types of cardiomyopathy because knowledge is lacking for how to tailor treatment plans for different genetic causes. Adult zebrafish (Danio rerio) have a higher throughout than rodents and are an emerging vertebrate model for studying cardiomyopathy. Herein, we review progress in the past decade that has proven the feasibility of this simple vertebrate for modeling inherited cardiomyopathies of distinct etiology, identifying effective therapeutic strategies for a particular type of cardiomyopathy, and discovering new cardiomyopathy genes or new therapeutic strategies via a forward genetic approach. On the basis of this progress, we discuss future research that would benefit from integrating this emerging model, including discovery of remaining causative genes and development of genotype-based therapies. Studies using this efficient vertebrate model are anticipated to significantly accelerate the implementation of precision medicine for inherited cardiomyopathies.