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 (dmd-MO). We use two approaches, muscle birefringence and muscle actin expression, to quantify muscle damage and show that the dmd-MO dystrophic phenotype closely resembles the zebrafish dmd mutant phenotype. We then show that the histone deacetylase (HDAC) inhibitor TSA, which has been shown to ameliorate the mdx mouse Duchenne model, can rescue muscle fiber damage in both dmd-MO and dmd mutant larvae. Our study identifies optimal morpholino and phenotypic scoring approaches for dystrophic zebrafish, further enhancing the zebrafish dmd model for rapid and cost-effective small molecule screening.
Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, Washington, USA.
Nathan M
NM
Johnson
Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, Washington, USA.
Gist H
GH
Farr
Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, Washington, USA; Department of Pediatrics, University of Washington, Seattle, Washington, USA.
Lisa
L
Maves