Mutation of Large, which encodes a putative glycosyltransferase, in an animal model of muscular dystrophy

ArticleinBiochimica et Biophysica Acta 1573(3):216-24 · January 2003with7 Reads
Impact Factor: 4.66 · DOI: 10.1016/S0304-4165(02)00387-2 · Source: PubMed

    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.