Cytoplasmic γ-actin expression in diverse animal models of muscular dystrophy

Abstract 

We recently showed that cytoplasmic γ-actin (γ_cyto-actin) is dramatically elevated in striated muscle of dystrophin-deficient mdx mice. Here, we demonstrate that γ_cyto-actin is markedly increased in golden retriever muscular dystrophy (GRMD), which better recapitulates the dystrophinopathy phenotype in humans. γ_cyto-Actin was also elevated in muscle from α-sarcoglycan null mice, but not in several other dystrophic animal models, including mice deficient in β-sarcoglycan, α-dystrobrevin, laminin-2, or α7 integrin. Muscle from mice lacking dystrophin and utrophin also expressed elevated γ_cyto-actin, which was not restored to normal by transgenic overexpression of α7 integrin. However, γ_cyto-actin was further elevated in skeletal muscle from GRMD animals treated with the glucocorticoid prednisone at doses shown to improve the dystrophic phenotype and muscle function. These data suggest that elevated γ_cyto-actin is part of a compensatory cytoskeletal remodeling program that may partially stabilize dystrophic muscle in some cases where the dystrophin–glycoprotein complex is compromised.

Keywords: Duchenne muscular dystrophy, mdx Mouse, GRMD dog, γ-Actin, Sarcoglycan, α-Dystrobrevin, α7 Integrin, Utrophin