title: Muscular dystrophy associated with alpha-dystroglycan deficiency in Sphynx and Devon Rex cats.
abstract: Recent studies have identified a number of forms of muscular dystrophy, termed dystroglycanopathies, which are associated with loss of natively glycosylated alpha-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 alpha-dystroglycan, while beta-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 alpha-dystroglycan protein, only a loss of protein expression. A reduction in laminin-alpha2 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 alpha-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 alpha-dystroglycan protein expression, and as such may represent a new type of dystroglycanopathy where expression, but not glycosylation, is affected.
authors.affiliation: Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Department of Pediatrics, Ohio State University, College of Medicine, Columbus, OH 43205, USA.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Martin
authors.forename: G Diane
authors.initials: GD
authors.lastname: Shelton
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Dickinson
authors.forename: Beverly K
authors.initials: BK
authors.lastname: Sturges
authors.forename: Rui
authors.initials: R
authors.lastname: Xu
authors.forename: Richard A
authors.initials: RA
authors.lastname: LeCouteur
authors.forename: Ling T
authors.initials: LT
authors.lastname: Guo
authors.forename: Robert A
authors.initials: RA
authors.lastname: Grahn
authors.forename: Harriet P
authors.initials: HP
authors.lastname: Lo
authors.forename: Kathryn N
authors.initials: KN
authors.lastname: North
authors.forename: Richard
authors.initials: R
authors.lastname: Malik
authors.forename: Eva
authors.initials: E
authors.lastname: Engvall
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Lyons
mesh_terms: D000818:Animals; D001706:Biopsy; D002415:Cats; D004195:Disease Models, Animal; D049030:Dystroglycans / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006031:Glycosylation; D015151:Immunoblotting; D007797:Laminin / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D008297:Male; D018908:Muscle Weakness / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology*; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016133:Polymerase Chain Reaction
chemical_list: C483081:DAG1 protein, human; D007797:Laminin; D037102:Lectins; D049030:Dystroglycans