The roles of laminin and its membrane receptors on muscular dystrophies

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Primary merosin-deficient congenital muscular dystrophy (CMD), which is caused by mutations in the 1aminin α2 chain gene, is characterized by marked dystrophic changes in skeletal muscles during early infancy. However little is known about the pathological process of the muscle fiber degeneration. We performed the immunohistochemical analysis of skeletal muscle in ten patients with primary merosin-deficient CMD using a panel of molecular markers for membrane proteins, cellular necrosis, and apoptosis. In the youngest patient (a 52 days old baby), prominent massive muscle cell degeneration occurred in association with the deposition of MAC, a marker of necrosis.In addition, we found scattered positive signals for apoptosis. Similar but milder changes were observed in six other patients younger than 1 year, but barely detectable in the patients older than 3 years. These findings imply that massive muscle fiber degeneration occurs in the very early stage of merosin-deficient CMD and may contribute to the severe dystrophic changes in muscle from early infancy.Fukuyama type congenital muscular dystrophy (FCMD) is characterized by severe dystrophic muscle wasting from early infancy with structural brain abnormalities. The FCMD gene encodes a novel protein named fukutin, but its function is not known yet. To elucidate the roles of fukutin, immunohistochemical and immunoblot analyses were performed in skeletal and cardiac muscles from patients with FCMD and controls. We found a selective deficiency of highly glycosylated α-dystroglycan (α-DG), but not β-DG, on the surface membrane of muscle fibers in patients with FCMD. Immunoblot analyses showed no immunoreactive band for α-DG, but positive for β-DG in FCMD. The present findings suggest a critical role for fukutin gene mutation in the loss or modification of glycosylation of α-DG, which may cause a crucial disruption of the transmembranous molecular linkage of muscle fibers in patients with FCMD.