title: Reduced proliferative activity of primary POMGnT1-null myoblasts in vitro.
abstract: Protein O-linked mannose beta1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) is an enzyme that transfers N-acetylglucosamine to O-mannose of glycoproteins. Mutations of the POMGnT1 gene cause muscle-eye-brain (MEB) disease. To obtain a better understanding of the pathogenesis of MEB disease, we mutated the POMGnT1 gene in mice using a targeting technique. The mutant muscle showed aberrant glycosylation of alpha-DG, and alpha-DG from mutant muscle failed to bind laminin in a binding assay. POMGnT1(-/-) muscle showed minimal pathological changes with very low-serum creatine kinase levels, and had normally formed muscle basal lamina, but showed reduced muscle mass, reduced numbers of muscle fibers, and impaired muscle regeneration. Importantly, POMGnT1(-/-) satellite cells proliferated slowly, but efficiently differentiated into multinuclear myotubes in vitro. Transfer of a retrovirus vector-mediated POMGnT1 gene into POMGnT1(-/-) myoblasts completely restored the glycosylation of alpha-DG, but proliferation of the cells was not improved. Our results suggest that proper glycosylation of alpha-DG is important for maintenance of the proliferative activity of satellite cells in vivo.
authors.affiliation: Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan. miyagoe@ncnp.go.jp
authors.forename: Yuko
authors.initials: Y
authors.lastname: Miyagoe-Suzuki
authors.forename: Nami
authors.initials: N
authors.lastname: Masubuchi
authors.forename: Kaori
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Michiko R
authors.initials: MR
authors.lastname: Wada
authors.forename: Shigeki
authors.initials: S
authors.lastname: Yuasa
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Saito
authors.forename: Kiichiro
authors.initials: K
authors.lastname: Matsumura
authors.forename: Hironori
authors.initials: H
authors.lastname: Kanesaki
authors.forename: Akira
authors.initials: A
authors.lastname: Kudo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Manya
authors.forename: Tamao
authors.initials: T
authors.lastname: Endo
authors.forename: Shin'ichi
authors.initials: S
authors.lastname: Takeda
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000097:blood; D053595:Embryonic Stem Cells / Q000378:metabolism; D005355:Fibrosis / Q000150:complications / Q000201:enzymology / Q000473:pathology; D017353:Gene Deletion; D018390:Gene Targeting; D007150:Immunohistochemistry; D051379:Mice; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D009137:Muscular Dystrophy, Animal / Q000097:blood / Q000150:complications / Q000201:enzymology / Q000473:pathology; D032446:Myoblasts / Q000166:cytology* / Q000201:enzymology* / Q000648:ultrastructure; D017351:N-Acetylglucosaminyltransferases / Q000172:deficiency* / Q000378:metabolism; D010641:Phenotype; D012038:Regeneration; D032496:Satellite Cells, Skeletal Muscle / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D015398:Signal Transduction
chemical_list: D017351:N-Acetylglucosaminyltransferases; C443106:protein O-mannose beta-1,2-N-acetylglucosaminyltransferase; D003402:Creatine Kinase