ABSTRACT
I t is now well established that mutations in the gene encoding the large sarcolemmal-associated protein dystrophin cause Duchenne and Becker muscular dystrophies (DMD and BMD). The core dystrophin glycoprotein complex (DGC) as described by the Campbell and Ozawa groups,1,2 is assembled around dystrophin, the lack of which has a dramatic effect upon the skeletal muscle of patients lacking the protein and also affects the heart and brain.3 In muscle, the core DGC is composed of at least 12 proteins (dystrophin, a - and P-dystroglycan, the sarcoglycans, sarcospan, the syntrophins and the (X-dystrobrevins) that form a molecular bridge between the actin-based cytoskeleton and laminin in the extracellular matrix (ECM). Patients lacking dystrophin have severely reduced levels of the DGC components at the sarcolemma whereas the levels of total cellular protein often remain unaltered. The effects of these alter ations on the normal physiological localization of the DGC may direcdy contribute to the complex pathology typically observed in dystrophin-deficient muscle.3
