title: Progressive muscle proteome changes in a clinically relevant pig model of Duchenne muscular dystrophy.
abstract: Duchenne muscular dystrophy (DMD) is caused by genetic deficiency of dystrophin and characterized by massive structural and functional changes of skeletal muscle tissue, leading to terminal muscle failure. We recently generated a novel genetically engineered pig model reflecting pathological hallmarks of human DMD better than the widely used mdx mouse. To get insight into the hierarchy of molecular derangements during DMD progression, we performed a proteome analysis of biceps femoris muscle samples from 2-day-old and 3-month-old DMD and wild-type (WT) pigs. The extent of proteome changes in DMD vs. WT muscle increased markedly with age, reflecting progression of the pathological changes. In 3-month-old DMD muscle, proteins related to muscle repair such as vimentin, nestin, desmin and tenascin C were found to be increased, whereas a large number of respiratory chain proteins were decreased in abundance in DMD muscle, indicating serious disturbances in aerobic energy production and a reduction of functional muscle tissue. The combination of proteome data for fiber type specific myosin heavy chain proteins and immunohistochemistry showed preferential degeneration of fast-twitch fiber types in DMD muscle. The stage-specific proteome changes detected in this large animal model of clinically severe muscular dystrophy provide novel molecular readouts for future treatment trials.
authors.affiliation: Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, Feodor-Lynen-Str. 25, D-81377 Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Fröhlich
authors.affiliation: Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Feodor-Lynen-Str. 25, D-81377 Munich, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kemter
authors.affiliation: Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, Feodor-Lynen-Str. 25, D-81377 Munich, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Flenkenthaler
authors.affiliation: Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Feodor-Lynen-Str. 25, D-81377 Munich, Germany.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Klymiuk
authors.affiliation: Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, Feodor-Lynen-Str. 25, D-81377 Munich, Germany.
authors.forename: Kathrin A
authors.initials: KA
authors.lastname: Otte
authors.affiliation: Institute of Veterinary Pathology, Centre for Clinical Veterinary Medicine, LMU Munich, Veterinärstr. 13, D-80539 Munich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Blutke
authors.affiliation: Friedrich-Baur-Institute, Department of Neurology, LMU Munich, Ziemssenstr. 1, D-80336 Munich, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Krause
authors.affiliation: Friedrich-Baur-Institute, Department of Neurology, LMU Munich, Ziemssenstr. 1, D-80336 Munich, Germany.
authors.forename: Maggie C
authors.initials: MC
authors.lastname: Walter
authors.affiliation: Institute of Veterinary Pathology, Centre for Clinical Veterinary Medicine, LMU Munich, Veterinärstr. 13, D-80539 Munich, Germany.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Wanke
authors.affiliation: Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, Feodor-Lynen-Str. 25, D-81377 Munich, Germany.|Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Feodor-Lynen-Str. 25, D-81377 Munich, Germany.
authors.forename: Eckhard
authors.initials: E
authors.lastname: Wolf
authors.affiliation: Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, Feodor-Lynen-Str. 25, D-81377 Munich, Germany.
authors.forename: Georg J
authors.initials: GJ
authors.lastname: Arnold
mesh_terms: D000375:Aging / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D016189:Dystrophin / Q000172:deficiency / Q000378:metabolism; D007150:Immunohistochemistry; D024101:Mitochondrial Proteins / Q000378:metabolism; D018656:Muscle Fibers, Fast-Twitch; D018657:Muscle Fibers, Slow-Twitch; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology*; D009137:Muscular Dystrophy, Animal / Q000378:metabolism* / Q000473:pathology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D020543:Proteome / Q000378:metabolism*; D034421:Sus scrofa
chemical_list: D016189:Dystrophin; D024101:Mitochondrial Proteins; D009124:Muscle Proteins; D020543:Proteome; D018995:Myosin Heavy Chains