δ-Sarcoglycan is required for early zebrafish muscle organization

Abstract

Mutations in sarcoglycans (α-, β-, γ-, and δ-) have been linked with limb girdle muscular dystrophy (LGMD) types 2C–F in humans. We have cloned the zebrafish orthologue encoding δ-sarcoglycan and mapped the gene to linkage group 21. The predicted zebrafish δ-sarcoglycan protein is highly homologous with its human orthologue including conservation of two of the three predicted glycosylation sites. Like other members of the dystrophin-associated protein complex (DAPC), δ-sarcoglycan localizes to the sarcolemmal membrane of the myofiber in adult zebrafish, but is more apparent at the myosepta in developing embryos. Zebrafish embryos injected with morpholinos against δ-sarcoglycan were relatively inactive at 5 dpf, their myofibers were disorganized, and swim bladders uninflated. Immunohistochemical and immunoblotting experiments show that δ-, β-, and γ-sarcoglycans were all downregulated in the morphants, whereas dystrophin expression was unaffected. Whereas humans lacking δ-sarcoglycan primarily show adult phenotypes, our results suggest that δ-sarcoglycan plays a role in early zebrafish muscle development.