Cytoplasmic gamma-actin expression in diverse animal models of muscular dystrophy.
We recently showed that cytoplasmic gamma-actin (gamma(cyto)-actin) is dramatically elevated in striated muscle of dystrophin-deficient mdx mice. Here, we demonstrate that gamma(cyto)-actin is markedly increased in golden retriever muscular dystrophy (GRMD), which better recapitulates the dystrophinopathy phenotype in humans. Gamma(cyto)-Actin was also elevated in muscle from alpha-sarcoglycan null mice, but not in several other dystrophic animal models, including mice deficient in beta-sarcoglycan, alpha-dystrobrevin, laminin-2, or alpha7 integrin. Muscle from mice lacking dystrophin and utrophin also expressed elevated gamma(cyto)-actin, which was not restored to normal by transgenic overexpression of alpha7 integrin. However, gamma(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 gamma(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.
Hanft
Laurin M
LM
Department of Physiology, University of Wisconsin, Madison, WI, United States.
Bogan
Daniel J
DJ
Mayer
Ulrike
U
Kaufman
Stephen J
SJ
Kornegay
Joe N
JN
Ervasti
James M
JM
D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003593:Cytoplasm / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology*; D039001:Integrin alpha Chains / Q000172:deficiency; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000473:pathology*; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000172:deficiency; D000075385:Netrins; D049031:Sarcoglycans / Q000145:classification / Q000172:deficiency
D000199:Actins; D039001:Integrin alpha Chains; D009419:Nerve Tissue Proteins; D000075385:Netrins; C456263:Ntng2 protein, mouse; D049031:Sarcoglycans