| The mdx mouse is an animal model for Duchenne muscular dystrophy (DMD), a disease caused by the absence of dystrophin. Although much has been done to elucidate the structure and function of dystrophin and the dystrophin-associated glycoprotein complex (DGC), little is known about the cascade of molecular events triggered by the absence of dystrophin that ultimately lead to muscle degeneration. To investigate the pathophysiological events, we analyzed alterations of protein expression in hindlimb muscles of three-month-old mdx mice using two-dimensional gel electrophoresis and mass spectrometry. This is the first analysis done of proteins in mdx skeletal muscle using a proteomics approach. Forty-six differentially expressed proteins from the cytosolic fraction of mdx hindlimb muscles were identified. Further we analyzed alterations of protein expression in mdx skeletal muscles at one-, and six-months of age to determine how protein expression changes with disease progression. The potential roles of the differentially expressed proteins are discussed in the context of the mdx phenotype.; Among the altered proteins identified from three-month-old mdx mice, adenylate kinase 1 (AK 1) and sensitive apoptotosis gene (SAG) were particularly interesting because of their dramatic changes in abundance and their important roles in maintaining muscle functions. Further biochemical and functional characterization of these proteins verified their roles in the response to the mdx genotype. Our results demonstrated the potential of functional proteomics for identifying important, unrecognized or neglected targets of disease and for providing insight into disease mechanism. |
