Zebrafishacta1bas a Candidate for Modeling Human Actin Cardiomyopathies

Abstract

AbstractHeart failure is the leading cause of mortality worldwide, primarily associated with cardiovascular disease. Many heart muscle diseases are caused by mutations in genes that encode contractile proteins, including cardiac actin mutations. Zebrafish are an advantageous system for modelling cardiac diseases due to their ability to develop without a functional heart throughout embryonic development. However, genome duplication in the teleost lineage poses a unique challenge by increasing the number of genes involved in heart development. Four actin genes are expressed in the zebrafish heart:acta1b, actc2, and duplicates ofactc1aon chromosomes 19 and 20. In this study, we characterize the actin genes involved in early zebrafish heart development usingin situhybridization and CRISPR targeting to determine the most suitable gene for modelling actin changes observed in human patients with heart disease. Theactc1aandacta1bgenes are predominantly expressed during embryonic heart development, resulting in severe cardiac phenotypes when targeted with CRISPR. Considering the duplication of theactc1agene, we recommendacta1bas the best gene for targeted cardiac actin research.