Skeletal muscle-specific ablation of gamma(cyto)-actin does not exacerbate the mdx phenotype.
We previously documented a ten-fold increase in gamma(cyto)-actin expression in dystrophin-deficient skeletal muscle and hypothesized that increased gamma(cyto)-actin expression may participate in an adaptive cytoskeletal remodeling response. To explore whether increased gamma(cyto)-actin fortifies the cortical cytoskeleton in dystrophic skeletal muscle, we generated double knockout mice lacking both dystrophin and gamma(cyto)-actin specifically in skeletal muscle (ms-DKO). Surprisingly, dystrophin-deficient mdx and ms-DKO mice presented with comparable levels of myofiber necrosis, membrane instability, and deficits in muscle function. The lack of an exacerbated phenotype in ms-DKO mice suggests gamma(cyto)-actin and dystrophin function in a common pathway. Finally, because both mdx and ms-DKO skeletal muscle showed similar levels of utrophin expression and presented with identical dystrophies, we conclude utrophin can partially compensate for the loss of dystrophin independent of a gamma(cyto)-actin-utrophin interaction.
Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota, United States of America.
Kurt W
KW
Prins
Dawn A
DA
Lowe
James M
JM
Ervasti
D000199:Actins / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002853:Chromatography, Liquid; D003593:Cytoplasm / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D018482:Muscle, Skeletal / Q000378:metabolism*; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype
D000199:Actins