Aberrant neuromuscular junctions and delayed terminal muscle fiber maturation in alpha-dystroglycanopathies
Abstract
Recent studies have revealed an association between post-translational modification of alpha-dystroglycan (alpha-DG) and certain congenital muscular dystrophies known as secondary alpha-dystroglycanopathies (alpha-DGpathies). Fukuyama-type congenital muscular dystrophy (FCMD) is classified as a secondary alpha-DGpathy because the responsible gene, fukutin, is a putative glycosyltransferase for alpha-DG. To investigate the pathophysiology of secondary alpha-DGpathies, we profiled gene expression in skeletal muscle from FCMD patients. cDNA microarray analysis and quantitative real-time polymerase chain reaction showed that expression of developmentally regulated genes, including myosin heavy chain (MYH) and myogenic transcription factors (MRF4, myogenin and MyoD), in FCMD muscle fibers is inconsistent with dystrophy and active muscle regeneration, instead more of implicating maturational arrest. FCMD skeletal muscle contained mainly immature type 2C fibers positive for immature-type MYH. These characteristics are distinct from Duchenne muscular dystrophy, suggesting that another mechanism in addition to dystrophy accounts for the FCMD skeletal muscle lesion. Immunohistochemical analysis revealed morphologically aberrant neuromusc...Continue Reading
References
Mutant glycosyltransferase and altered glycosylation of alpha-dystroglycan in the myodystrophy mouse
Post-translational disruption of dystroglycan-ligand interactions in congenital muscular dystrophies
Citations
Molecular interaction between fukutin and POMGnT1 in the glycosylation pathway of alpha-dystroglycan
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