title: Autophagy in a mouse model of distal myopathy with rimmed vacuoles or hereditary inclusion body myopathy.
abstract: Distal myopathy with rimmed vacuoles (DMRV) or hereditary inclusion body myopathy (hIBM) is an autosomal recessive disorder clinically characterized by weakness that initially involves the distal muscles, although other muscles can be affected as well. Pathological hallmarks include the presence of rimmed vacuoles (RVs) and intracellular Congo red-positive depositions in vacuolated or nonvacuolated fibers. Mutations in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene, which encodes the rate-limiting enzyme in sialic acid biosynthesis, are causative of DMRV/hIBM. Recently, we have generated a mouse model (Gne(-/-)hGNEV572L-Tg) for this disease, and have shown that these mice exhibit hyposialylation and intracellular amyloid deposition before the characteristic RVs are detected, indicating that autophagy is a downstream phenomenon to hyposialylation and amyloid deposition in DMRV/hIBM.
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
authors.forename: May Christine V
authors.initials: MC
authors.lastname: Malicdan
authors.forename: Satoru
authors.initials: S
authors.lastname: Noguchi
authors.forename: Ichizo
authors.initials: I
authors.lastname: Nishino
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D004195:Disease Models, Animal; D049310:Distal Myopathies / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000235:genetics; D009154:Mutation; D018979:Myositis, Inclusion Body / Q000235:genetics* / Q000473:pathology*; D019158:N-Acetylneuraminic Acid / Q000096:biosynthesis; D014617:Vacuoles / Q000473:pathology* / Q000648:ultrastructure
chemical_list: D016229:Amyloid beta-Peptides; D009097:Multienzyme Complexes; C482901:UDP-N-acetylglucosamine 2-epimerase - N-acetylmannosamine kinase; D019158:N-Acetylneuraminic Acid