The HDAC Inhibitor TSA Ameliorates a Zebrafish Model of Duchenne Muscular Dystrophy

Zebrafish are an excellent model for Duchenne muscular dystrophy. In particular, zebrafish provide a system for rapid, easy, and low-cost screening of small molecules that can ameliorate muscle damage in dystrophic larvae. Here we identify an optimal anti-sense morpholino cocktail that robustly knocks down zebrafish Dystrophin (<i>dmd</i>-MO). We use two approaches, muscle birefringence and muscle actin expression, to quantify muscle damage and show that the <i>dmd</i>-MO dystrophic phenotype closely resembles the zebrafish <i>dmd</i> mutant phenotype. We then show that the histone deacetylase (HDAC) inhibitor TSA, which has been shown to ameliorate the <i>mdx</i> mouse Duchenne model, can rescue muscle fiber damage in both <i>dmd</i>-MO and <i>dmd</i> mutant larvae. Our study identifies optimal morpholino and phenotypic scoring approaches for dystrophic zebrafish, further enhancing the zebrafish <i>dmd</i> model for rapid and cost-effective small molecule screening.