Figure 1.

Dystrophin-independent muscle improvement in sapje-like fish. Compounds targeting the heme oxygenase pathway found to be efficacious in sapje models of DMD were each administered to forty offspring of heterozygous sapje-like matings. Following 4 days of treatment, fish genotypes, muscle phenotypes and dystrophin expression were determined using Sanger sequencing, birefringence and immunostaining, respectively. (A) Efficacious drugs identified in high-throughput zebrafish screens converge on the heme oxygenase pathway. (B) Immunohistochemistry of the muscle of dystrophin^−/− fish demonstrates that muscle improvement is independent of dystrophin expression. WT, wild type; NT, non-treatment and drug treatment listed. (C) 30–90% of dystrophin^−/− fish were restored in at 4 dpf (P = 1.49e-02, chi² test). Cerulenin was the most efficacious drug with 90% recovery rate (P < 1e-07, two proportion test).