We recently showed that cytoplasmic γ-actin (γcyto-actin) is dramatically elevated in striated muscle of dystrophin-deficient mdx mice. Here, we demonstrate that γcyto-actin is markedly increased in golden retriever muscular dystrophy (GRMD), which better recapitulates the dystrophinopathy phenotype in humans. γcyto-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 γcyto-actin, which was not restored to normal by transgenic overexpression of α7 integrin. However, γcyto-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 γcyto-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.
Bibliographical noteFunding Information:
We thank R. Mark Grady for α-dystrobrevin null mice, Kevin P. Campbell for α- and β-sarcoglycan null mice, and Kevin Sonnemann and Michele Jaeger for their critiques. Supported by grants from the MDA (J.M.E. and S.J.K.) and NIH (AR049899 and AR042423 to J.M.E., AG014632 to S.J.K.).
- Duchenne muscular dystrophy
- GRMD dog
- mdx Mouse
- α7 Integrin