alpha- and beta-dystroglycan (DG) were first identified as members of an oligomeric, transmembrane complex expressed in muscle and linking laminin (LN) in the extracellular matrix (ECM) to dystrophin in the submembraneous cytoskeleton. This dystrophin-associated glycoprotein complex (DGC) has been proposed to perform a structural role in skeletal muscle, its loss leading to loss of membrane integrity, muscle fiber degeneration and muscular dystrophy. alpha- and beta-DG appear to form the core of the DGC since alpha-DG is a high affinity LN receptor while beta-DG is a transmembrane protein that anchors alpha-DG to the membrane and interacts with dystrophin intracellularly. In order to determine the involvement of DG in skeletal muscle homeostasis and in LN assembly, we generated mouse muscle cell lines deficient in DG expression. Extensive characterization of these cells revealed that DG is essential for LN assembly on the surface of mature myotubes but that it is not involved in the maintenance of membrane integrity in culture. However, DG-deficient cells show increased apoptotic cell death during and after the period of myoblast differentiation into myotubes, indicating that DG is important for muscle cell survival.