The mdx mouse is the most commonly used 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 lead to muscle degeneration. To study the molecular basis of DMD, we decided to systematically study the skeletal muscle
proteome in mdx mice at different ages. By using two-dimensional (2-D) gel electrophoresis, we defined changes in the
protein expression pattern between mdx and control muscles. Approximately 46 differentially expressed
proteins from the cytosolic fraction of mdx hindlimb muscles at three months of age were detected by 2-D gel analysis, of which 24 were identified by matrix assisted
laser desorption/ionization- mass spectrometry. Most of the
proteins fell into five groups of functionally related
proteins. These functional categories are (i) metabolism and energy production, (ii)
serine protease inhibitor family, (iii) growth and differentiation, (iv)
calcium homeostasis, and (v) cytoskeletal reorganization and biogenesis. The potential roles of the differentially expressed
proteins are discussed in the context of the mdx phenotype. Finally, we analyzed alterations of
protein expression in mdx mice at one and six months of age to determine how
protein expression changes with
disease progression.