Aberrant glycosylation of α-dystroglycan causes defective binding of laminin in the muscle of chicken muscular dystrophy

Dystroglycan is a central component of dystrophin–glycoprotein complex that links extracellular matrix and cytoskeleton in skeletal muscle. Although dystrophic chicken is well established as an animal model of human muscular dystrophy, the pathomechanism leading to muscular degeneration remains unknown. We show here that glycosylation and laminin-binding activity of α-dystroglycan (α-DG) are defective in dystrophic chicken. Extensive glycan structural analysis reveals that Galβ1-3GalNAc and GalNAc residues are increased while Siaα2-3Gal structure is reduced in α-DG of dystrophic chicken. These results implicate aberrant glycosylation of α-DG in the pathogenesis of muscular degeneration in this model animal of muscular dystrophy.