title: Quantitative proteomic analysis of dystrophic dog muscle.
abstract: Duchenne muscular dystrophy (DMD) is caused by null mutations in the dystrophin gene, leading to progressive and unrelenting muscle loss. Although the genetic basis of DMD is well resolved, the cellular mechanisms associated with the physiopathology remain largely unknown. Increasing evidence suggests that secondary mechanisms, as the alteration of key signaling pathways, may play an important role. In order to identify reliable biomarkers and potential therapeutic targets, and taking advantage of the clinically relevant Golden Retriever Muscular Dystrophy (GRMD) dog model, a proteomic study was performed. Isotope-coded affinity tag (ICAT) profiling was used to compile quantitative changes in protein expression profiles of the vastus lateralis muscles of 4-month old GRMD vs healthy dogs. Interestingly, the set of under-expressed proteins detected appeared primarily composed of metabolic proteins, many of which have been shown to be regulated by the transcriptional peroxisome proliferator-activated receptor-gamma co-activator 1 alpha (PGC-1α). Subsequently, we were able to showed that PGC1-α expression is dramatically reduced in GRMD compared to healthy muscle. Collectively, these results provide novel insights into the molecular pathology of the clinically relevant animal model of DMD, and indicate that defective energy metabolism is a central hallmark of the disease in the canine model.
authors.affiliation: CNRS UMR6204, Faculté des Sciences et des Techniques, F-44322 Nantes Cedex 3, France. laetitia.guevel@univ-nantes.fr
authors.forename: Laetitia
authors.initials: L
authors.lastname: Guevel
authors.forename: Jessie R
authors.initials: JR
authors.lastname: Lavoie
authors.forename: Carolina
authors.initials: C
authors.lastname: Perez-Iratxeta
authors.forename: Karl
authors.initials: K
authors.lastname: Rouger
authors.forename: Laurence
authors.initials: L
authors.lastname: Dubreil
authors.forename: Marie
authors.initials: M
authors.lastname: Feron
authors.forename: Sophie
authors.initials: S
authors.lastname: Talon
authors.forename: Marjorie
authors.initials: M
authors.lastname: Brand
authors.forename: Lynn A
authors.initials: LA
authors.lastname: Megeney
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D004285:Dogs; D004734:Energy Metabolism / Q000502:physiology*; D015151:Immunoblotting; D007150:Immunohistochemistry; D013058:Mass Spectrometry; D018482:Muscle, Skeletal / Q000378:metabolism*; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D015415:Biomarkers; D017931:DNA Primers; D020543:Proteome; D015534:Trans-Activators