title: A rapid PCR method for genotyping the Large(myd) mouse, a model of glycosylation-deficient congenital muscular dystrophy.
abstract: The myodystrophy (Large(myd)) mouse has a spontaneous loss of function mutation in a putative glycosyltransferase gene (Large). Mutations in the human gene (LARGE) have been described in congenital muscular dystrophy type 1D (MDC1D). Mutations in four other genes that encode known or putative glycosylation enzymes (POMT1, POMGnT1, fukutin and FKRP) are also associated with muscular dystrophy. In all these diseases hypoglycosylation of alpha-dystroglycan, and consequent loss of ligand binding, is a common pathomechanism. Currently, the Large(myd) mouse is the principal animal model for studying the underlying molecular mechanisms of this group of disorders. Over-expression of LARGE in cells from patients with mutations in POMT1 or POMGnT1 results in hyperglycosylation of alpha-dystroglycan and restoration of laminin binding. Thus, LARGE is a potential therapeutic target. Here, we define the intronic deletion breakpoints of the Large(myd) mutation and describe a simple, PCR-based diagnostic assay, facilitating the study of this important animal model.
authors.affiliation: Institute of Genetics, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK.
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Browning
authors.forename: Prabhjit K
authors.initials: PK
authors.lastname: Grewal
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Moore
authors.forename: Jane E
authors.initials: JE
authors.lastname: Hewitt
mesh_terms: D000818:Animals; D003001:Cloning, Molecular / Q000379:methods; D004195:Disease Models, Animal; D005838:Genotype; D006031:Glycosylation; D016695:Glycosyltransferases / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D051379:Mice; D009137:Muscular Dystrophy, Animal / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D009223:Myotonic Dystrophy / Q000175:diagnosis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011485:Protein Binding / Q000502:physiology
chemical_list: D016695:Glycosyltransferases