Using Zebrafish to Characterize Cardiomyopathy Related Mutations in the Cardiac Actin Gene
Over the last decade, the zebrafish (Danio rerio) has emerged as a model organism for cardiovascular research. My research is directed toward using zebrafish as a model for determining the molecular mechanisms of cardiomyopathy development linked to mutations in the cardiac actin gene (ACTC). To characterize the zebrafish system as an in vivo model, misexpression of human ACTC mRNA and knockdown of endogenous zebrafish actc1a expression with morpholinos were studied. Traditional injections of ACTC mRNA into the yolk did not result in protein misexpression; however, when mRNA is injected directly into the cell, an increase in protein misexpression occurred. Knockdown studies revealed a significantly decreased heart rate and a heart and tail phenotype. Rescue attempts by co-injection of ACTC mRNA were not successful, likely due to the additive effects of the misexpression of ACTC protein. Nevertheless, future work shows promise for using zebrafish as a model of cardiovascular disease.