title: Postnatal muscle modification by myogenic factors modulates neuropathology and survival in an ALS mouse model.
abstract: MyoD and myogenin are myogenic transcription factors preferentially expressed in adult fast and slow muscles, respectively. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder in which motor neuron loss is accompanied by muscle denervation and paralysis. Studies suggest that muscle phenotype may influence ALS disease progression. Here we demonstrate that myogenin gene transfer into muscle supports spinal cord motor neuron survival and muscle endplate innervation in the G93A SOD1 fALS mice. On the other hand, MyoD gene transfer decreases survival and enhances motor neuron degeneration and muscle denervation. Although an increase in motor neuron count is associated with increased succinic dehydrogenase staining in the muscle, muscle overexpression of PGC-1α does not improve survival or motor function. Our study suggests that postnatal muscle modification influences disease progression and demonstrates that the muscle expression of myogenic and metabolic regulators differentially impacts neuropathology associated with disease progression in the G93A SOD1 fALS mouse model.
authors.affiliation: Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4.
authors.forename: Kevin H J
authors.initials: KH
authors.lastname: Park
authors.affiliation: Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4.
authors.forename: Sonia
authors.initials: S
authors.lastname: Franciosi
authors.affiliation: 1] Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4 [2] Division of Neurology, Department of Medicine, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4.
authors.forename: Blair R
authors.initials: BR
authors.lastname: Leavitt
mesh_terms: D000367:Age Factors; D000690:Amyotrophic Lateral Sclerosis / Q000503:physiopathology*; D000818:Animals; D002470:Cell Survival / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D018014:Gene Transfer Techniques; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000294:innervation / Q000503:physiopathology*; D017570:MyoD Protein / Q000008:administration & dosage / Q000235:genetics*; D018008:Myogenin / Q000235:genetics* / Q000378:metabolism; D045442:Rotarod Performance Test; D013116:Spinal Cord / Q000473:pathology
chemical_list: D017570:MyoD Protein; D018008:Myogenin