Skeletal Muscle-Specific Ablation of γ(cyto)-Actin Does Not Exacerbate the mdx Phenotype

We previously documented a ten-fold increase in γ(cyto)-actin expression in dystrophin-deficient skeletal muscle and hypothesized that increased γ(cyto)-actin expression may participate in an adaptive cytoskeletal remodeling response. To explore whether increased γ(cyto)-actin fortifies the cortical cytoskeleton in dystrophic skeletal muscle, we generated double knockout mice lacking both dystrophin and γ(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 γ(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 γ(cyto)-actin-utrophin interaction.