Duchenne muscular dystrophy: deficiency of dystrophin-associated proteins in the sarcolemma

Abstract

Dystrophin, the protein product of the Duchenne muscular dystrophy (DMD) gene, is a major component of the subsarcolemmal cytoskeleton and exists in a large oligomeric complex tightly associated with several sarcolemmal glycoproteins which provide a linkage to the extracellular matrix protein, laminin. In the present study, we investigated the status of the dystrophin-associated proteins in the skeletal muscle from 17 DMD patients of various ages. The results revealed a dramatic reduction in all of the dystrophin-associated proteins in the sarcolemma of DMD muscle compared with normal muscle and muscle from a variety of other neuromuscular diseases. This abnormality was common in all 17 DMD patients, irrespective of age. Our results indicate that the absence of dystrophin leads to the loss in all of the dystrophin-associated proteins, which renders DMD muscle fibers susceptible to necrosis. The analysis of dystrophin-associated proteins is important in the assessment of experimental therapies that attempt to replace dystrophin in DMD muscle.