title: Mutation of Large, which encodes a putative glycosyltransferase, in an animal model of muscular dystrophy.
abstract: The myodystrophy (myd) mutation arose spontaneously and has an autosomal recessive mode of inheritance. Homozygous mutant mice display a severe, progressive muscular dystrophy. Using a positional cloning approach, we identified the causative mutation in myd as a deletion within the Large gene, which encodes a putative glycosyltransferase with two predicted catalytic domains. By immunoblotting, the alpha-subunit of dystroglycan, a key muscle membrane protein, is abnormal in myd mice. This aberrant protein might represent altered glycosylation of the protein and contribute to the muscular dystrophy phenotype. Our results are discussed in the light of recent reports describing mutations in other glycosyltransferase genes in several forms of human muscular dystrophy.
authors.affiliation: Institute of Genetics, Queen's Medical Centre, The University of Nottingham, UK.
authors.forename: Prabhjit K
authors.initials: PK
authors.lastname: Grewal
authors.forename: Jane E
authors.initials: JE
authors.lastname: Hewitt
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003598:Cytoskeletal Proteins / Q000378:metabolism / Q000502:physiology; D049030:Dystroglycans; D006031:Glycosylation; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology; D051379:Mice; D018101:Mice, Inbred mdx; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000201:enzymology* / Q000235:genetics; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000502:physiology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D010641:Phenotype
chemical_list: D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D049030:Dystroglycans; C117674:LARGE1 protein, human; D017351:N-Acetylglucosaminyltransferases