Why the study?
Genome duplication in teleost zebrafish complicates identifying the most suitable actin gene for modeling human actin-related cardiomyopathies.
The zebrafish acta1b gene is the optimal candidate for introducing and studying human actin mutations to model cardiomyopathies, avoiding the complications of the duplicated actc1a gene.
acta1b targeting offers a viable zebrafish model for actin cardiomyopathies; leaves open translation to human disease pending further validation.
Heart 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 of actc1a on chromosomes 19 and 20. In this study, we characterize the actin genes involved in early zebrafish heart development using in situ hybridization and CRISPR targeting to determine the most suitable gene for modelling actin changes observed in human patients with heart disease. The actc1a and acta1b genes are predominantly expressed during embryonic heart development, resulting in severe cardiac phenotypes when targeted with CRISPR. Considering the duplication of the actc1a gene, we recommend acta1b as the best gene for targeted cardiac actin research.
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Prill et al. (2023) studied this question.
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