Laminin-alpha 2 but not -alpha 1-mediated adhesion of human (Duchenne) and murine (mdx) dystrophic myotubes is seriously defective

It has been suggested that alpha-dystroglycan links the dystrophin-associated protein complex and extracellular matrix and that the absence of dystrophin and alpha-dystroglycan in Duchenne muscular dystrophy (DMD) may lead to the break-down of this linkage, In the present study, myotubes from DMD patients and murine X-linked muscular dystrophic mice (mdx) were used to measure their adhesive force to the physiological laminin-alpha 2 substrate, and it was found that the dystrophic myotubes were selectively unable to sustain adhesion, However, normal and dystrophic myotubes attached equally well to the laminin-alpha 1 substrate. As far as we know, this is the first experimental evidence that the absence of dystrophin causes the complete loss of a still unknown laminin-alpha 2-dependent adhesion force, therefore suggesting that the primary consequence of Duchenne dystrophy consists of the loss of an authentic mechanical linkage at the level of the alpha-dystroglycan/basal lamina interface. (C) 1997 Federation of European Biochemical Societies.