Duchenne muscular dystrophy (DMD) is caused by the absence of a functional dystrophin protein and is modeled by the mdx mouse. The mdx mouse suffers an early necrotic bout in the hind limb muscles lasting from approximately 4 to 7 weeks. The purpose of this investigation was to determine the extent to which dystrophin deficiency changed the proteome very early in the disease process. In order to accomplish this, proteins from gastrocnemius from 6-week-old C57 (n = 6) and mdx (n = 6) mice were labeled with fluorescent dye and subjected to two-dimensional differential in-gel electrophoresis (2D-DIGE). Resulting differentially expressed spots were excised and protein identity determined via MALDI-TOF followed by database searching using MASCOT. Proteins of the immediate energy system and glycolysis were generally down-regulated in mdx mice compared to C57 mice. Conversely, expression of proteins involved in the Kreb's cycle and electron transport chain were increased in dystrophin-deficient muscle compared to control. Expression of cytoskeletal components, including tubulins, vimentin, and collagen, were increased in mdx mice compared to C57 mice. Importantly, these changes are occurring at only 6 weeks of age and are caused by acute dystrophin deficiency rather than more chronic injury. These data may provide insight regarding early pathologic changes occurring in dystrophin-deficient skeletal muscle.

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Duchenne muscular dystrophy (DMD), the most common, fatal, X‐linked disease, is caused by a defect in the dystrophin gene. While dystrophin deficiency is the causative factor in this disease, changes in the expression of other proteins may also contribute to disease pathology. The objective of this investigation was to determine the extent to which dystrophin deficiency impacts the muscle proteome. We performed two dimensional differential in‐gel electrophoresis (2D‐DIGE) (pH 4‐7) on gastrocnemii taken from 6 week old male mice (n=6 mdx; n=6 C57). Of a total of 2200 spots detected, 41 spots (representing unique isoforms or modified proteins) were found to be differentially expressed (p<0.1; 24 spots with p<0.05). Of these, 30 spots were increased and 11 were decreased in mdx compared to control. Using mass spectroscopy and MALDI‐TOF, the identity of the proteins represented was confirmed in 36 spots. These proteins represent a variety of cell functions including apoptosis, mitochondrial function, and cell growth and differentiation. Further analysis of these proteins may allow for the identification of novel pathways and lead to the development of innovative strategies to minimize disease progression.