title: Proteomics reveals drastic increase of extracellular matrix proteins             collagen and dermatopontin in the aged mdx diaphragm model of Duchenne muscular             dystrophy.
abstract: Duchenne muscular dystrophy is a lethal genetic disease of childhood caused             by primary abnormalities in the gene coding for the membrane cytoskeletal protein             dystrophin. The mdx mouse is an established animal model of various aspects of             X-linked muscular dystrophy and is widely used for studying fundamental mechanisms             of dystrophinopathy and testing novel therapeutic approaches to treat one of the             most frequent gender-specific diseases in humans. In order to determine global             changes in the muscle proteome with the progressive deterioration of mdx tissue             with age, we have characterized diaphragm muscle from mdx mice at three ages (8-weeks,             12-months and 22-months) using mass spectrometry-based proteomics. Altered expression             levels in diaphragm of 8-week vs. 22-month mice were shown to occur in 11 muscle-associated             proteins. Aging in the mdx diaphragm seems to be associated with a drastic increase             in the extracellular matrix proteins, collagen and dermatopontin, the molecular             chaperone αB-crystallin, and the intermediate filament protein vimentin, suggesting             increased accumulation of connective tissue, an enhanced cellular stress response             and compensatory stabilization of the weakened membrane cytoskeleton. These proteomic             findings establish the aged mdx diaphragm as an excellent model system for studying             secondary effects of dystrophin deficiency in skeletal muscle tissue.
authors.affiliation: Department of Biology, National University of Ireland, Maynooth,                     Kildare, Republic of Ireland.
authors.forename: Steven
authors.initials: S
authors.lastname: Carberry
authors.forename: Margit
authors.initials: M
authors.lastname: Zweyer
authors.forename: Dieter
authors.initials: D
authors.lastname: Swandulla
authors.forename: Kay
authors.initials: K
authors.lastname: Ohlendieck
mesh_terms: D000367:Age Factors; D000818:Animals; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism*; D003964:Diaphragm / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D013058:Mass Spectrometry; D051379:Mice; D018101:Mice, Inbred mdx; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism; D040901:Proteomics
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; C504453:Dpt protein, mouse; D016326:Extracellular Matrix Proteins; D020543:Proteome; D003094:Collagen