The expression of dystrophin, the dystrophin-associated proteins and utrophin has been studied immunocytochemically in three young, manifesting carriers of Duchenne muscular dystrophy, aged 3, 5 and 12 yrs, one adult manifesting carrier, aged 60 yrs, and one presumptive carrier with a raised serum creatine kinase, aged 24 yrs, the mother of the 5-yr-old manifesting carrier. The manifesting carr...

BACKGROUND The localization of dystrophin at the sarcolemma of cardiac skeletal fibers and cardiac Purkinje fibers has been described. Dystrophin deficiency produces clinical manifestations of disease in skeletal muscles and hearts of patients with Duchenne and Becker muscular dystrophy. Utrophin (or dystrophin-related protein), a dystrophin homologous protein, was found to be expressed in feta...

Dystrophin, the protein product of the Duchenne muscular dystrophy (DMD) gene, is a cytoskeletal protein tightly associated with a large oligomeric complex of sarcolemmal glycoproteins including dystroglycan, which provides a linkage to the extracellular matrix component, laminin. In DMD, the absence of dystrophin leads to a drastic reduction in all of the dystrophin-associated proteins, causin...

Dystrophin, the protein product of the Duchenne muscular dystrophy (DMD) gene locus, is expressed on the muscle fiber surface. One key to further understanding of the cellular function of dystrophin would be extended knowledge about its subcellular organization. We have shown that dystrophin molecules are not uniformly distributed over the humen, rat, and mouse skeletal muscle fiber surface usi...

Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene. Therapeutic gene replacement of a dystrophin cDNA into dystrophic muscle can provide functional dystrophin protein to the tissue. However, vector-mediated gene transfer is limited by anti-vector and anti-transgene host immunity that causes rejection of the therapeutic protein. We hypothesized that rapamycin (RAPA) ...

The possibility of an interaction between the cytoskeletal protein dystrophin and cell surface caveolae in the mammalian myocardium was investigated by several techniques. Caveolin (cav)-3-enriched, detergent-insoluble membranes isolated from purified ventricular sarcolemma by density-gradient fractionation were found to contain dystrophin and dystroglycan. Further purification of cav-3-contain...

Dystrophin, the protein product of the human Duchenne muscular dystrophy gene, exists in skeletal muscle as a large oligomeric complex that contains four glycoproteins of 156, 50, 43, and 35 kD and a protein of 59 kD. Here, we investigated the relative abundance of each of the components of the dystrophin-glycoprotein complex in skeletal muscle from normal and mdx mice, which are missing dystro...

Duchenne muscular dystrophy (DMD), the most common inherited neuromuscular disorder, is characterized by progressive muscle wasting and weakness. One third of Duchenne patients suffer a moderate to severe, nonprogressive form of mental retardation. Mutations in the DMD gene are thought to be responsible, with the shorter isoforms of dystrophin implicated in its molecular brain pathogenesis. It ...

Mutations in dystrophin lead to Duchenne muscular dystrophy, which is among the most common human genetic disorders. Dystrophin nucleates assembly of the dystrophin-glycoprotein complex (DGC), and a defective DGC disrupts an essential link between the intracellular cytoskeleton and the basal lamina, leading to progressive muscle wasting. In vitro studies have suggested that dystrophin phosphory...

Duchenne muscular dystrophy (DMD) is a severe muscle-wasting disease with unmet medical need. The disease is caused by mutations that disrupt the open reading frame of the dystrophin protein that is required to maintain muscle fiber stability during contraction. Lacking dystrophin patients' muscle fibers are continuously damaged eventually leading to replacement of muscle tissue by fibrotic and...