skeletal muscle-specific ablation of γcyto-actin does not exacerbate the mdx phenotype骨骼阳性消融γcyto-actin不会加剧mdx表型.pdf

Skeletal Muscle-Specific Ablation of ccyto-Actin Does Not Exacerbate the mdx Phenotype 1 2 1 Kurt W. Prins , Dawn A. Lowe , James M. Ervasti * 1 Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota, United States of America, 2 Department of Physical Medicine and Rehabilitation, University of Minnesota, Minneapolis, Minnesota, United States of America Abstract We previously documented a ten-fold increase in ccyto-actin expression in dystrophin-deficient skeletal muscle and hypothesized that increased ccyto-actin expression may participate in an adaptive cytoskeletal remodeling response. To explore whether increased ccyto-actin fortifies the cortical cytoskeleton in dystrophic skeletal muscle, we generated double knockout mice lacking both dystrophin and ccyto-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 ccyto-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 ccyto-actin-utrophin interaction. Citation: Prins KW, Lowe DA, Ervasti JM (2008) Skeletal Muscle-Specific Ablation of ccyto-Actin Does Not Exacerbate the mdx Phenotype. PLoS ONE 3(6): e2419. doi:10.1371/journal.pone.0002419 Editor: Antoni L. Andreu, Hospital Vall d’Hebron, Spain Received April 7, 2008; Accepted May 8, 2008; Published June 11, 2008