Muscular dystrophy associated with α-dystroglycan deficiency in Sphynx and Devon Rex cats

Paul T. Martin, G. Diane Shelton, Peter J Dickinson, Beverly Sturges, Rui Xu, Richard A Lecouteur, Ling T. Guo, Robert A Grahn, Harriet P. Lo, Kathryn N. North, Richard Malik, Eva Engvall, Leslie A Lyons

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Recent studies have identified a number of forms of muscular dystrophy, termed dystroglycanopathies, which are associated with loss of natively glycosylated α-dystroglycan. Here we identify a new animal model for this class of disorders in Sphynx and Devon Rex cats. Affected cats displayed a slowly progressive myopathy with clinical and histologic hallmarks of muscular dystrophy including skeletal muscle weakness with no involvement of peripheral nerves or CNS. Skeletal muscles had myopathic features and reduced expression of α-dystroglycan, while β-dystroglycan, sarcoglycans, and dystrophin were expressed at normal levels. In the Sphynx cat, analysis of laminin and lectin binding capacity demonstrated no loss in overall glycosylation or ligand binding for the α-dystroglycan protein, only a loss of protein expression. A reduction in laminin-α2 expression in the basal lamina surrounding skeletal myofibers was also observed. Sequence analysis of translated regions of the feline dystroglycan gene (DAG1) in affected cats did not identify a causative mutation, and levels of DAG1 mRNA determined by real-time QRT-PCR did not differ significantly from normal controls. Reduction in the levels of glycosylated α-dystroglycan by immunoblot was also identified in an affected Devon Rex cat. These data suggest that muscular dystrophy in Sphynx and Devon Rex cats results from a deficiency in α-dystroglycan protein expression, and as such may represent a new type of dystroglycanopathy where expression, but not glycosylation, is affected.

Original languageEnglish (US)
Pages (from-to)942-952
Number of pages11
JournalNeuromuscular Disorders
Volume18
Issue number12
DOIs
StatePublished - Dec 2008

Keywords

  • Devon Rex
  • Dystroglycan
  • Feline
  • Glycosylation
  • Muscular Dystrophy
  • Neuromuscular
  • Sphynx

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health
  • Genetics(clinical)
  • Neurology

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