Association of dystrophin-related protein with dystrophin-associated proteins in mdx mouse muscle

Abstract

DYSTROPHIN is associated with a complex of muscle membrane (sarcolemmal) glycoproteins that provide a linkage to the extracellular matrix protein, laminin1-8. The absence of dystrophin leads to a dramatic reduction of the dystrophin-associated proteins (156DAG, 59DAP, 50DAG, 43DAG and 35DAG) in the sarcolemma of patients with Duchenne muscular dystrophy and mdx mice 2,6-8. Here we demonstrate that dystrophin-related protein (DRP, utrophin), an autosomal homologue of dystrophin9,17, is associated with an identical or antigenically similar complex of sarcolemmal proteins and that DRP and the dystrophin/DRP-associated proteins colocalize to the neuromuscular junction in Duchenne muscular dystrophy and mdx muscle. The DRP and dystrophin/DRP-associated proteins are found throughout the sarcolemma in small-calibre skeletal muscles and cardiac muscle of adult mdx mice. Because these muscles show minimal pathological changes18-20, our results could provide a basis for the upregulation of DRP as a potential therapeutic approach. © 1992 Nature Publishing Group.