title: CuZnSOD gene deletion targeted to skeletal muscle leads to loss of contractile force but does not cause muscle atrophy in adult mice.
abstract: We have previously shown that deletion of CuZnSOD in mice (Sod1(-/-) mice) leads to accelerated loss of muscle mass and contractile force during aging. To dissect the relative roles of skeletal muscle and motor neurons in this process, we used a Cre-Lox targeted approach to establish a skeletal muscle-specific Sod1-knockout (mKO) mouse to determine whether muscle-specific CuZnSOD deletion is sufficient to cause muscle atrophy. Surprisingly, mKO mice maintain muscle masses at or above those of wild-type control mice up to 18 mo of age. In contrast, maximum isometric specific force measured in gastrocnemius muscle is significantly reduced in the mKO mice. We found no detectable increases in global measures of oxidative stress or ROS production, no reduction in mitochondrial ATP production, and no induction of adaptive stress responses in muscle from mKO mice. However, Akt-mTOR signaling is elevated and the number of muscle fibers with centrally located nuclei is increased in skeletal muscle from mKO mice, which suggests elevated regenerative pathways. Our data demonstrate that lack of CuZnSOD restricted to skeletal muscle does not lead to muscle atrophy but does cause muscle weakness in adult mice and suggest loss of CuZnSOD may potentiate muscle regenerative pathways.
authors.affiliation: Department of Physiology, University of Texas Health Science Center, San Antonio, Texas 78249, USA.
authors.forename: Yiqiang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Carol
authors.initials: C
authors.lastname: Davis
authors.forename: George K
authors.initials: GK
authors.lastname: Sakellariou
authors.forename: Yun
authors.initials: Y
authors.lastname: Shi
authors.forename: Anna C
authors.initials: AC
authors.lastname: Kayani
authors.forename: Daniel
authors.initials: D
authors.lastname: Pulliam
authors.forename: Arunabh
authors.initials: A
authors.lastname: Bhattacharya
authors.forename: Arlan
authors.initials: A
authors.lastname: Richardson
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Jackson
authors.forename: Anne
authors.initials: A
authors.lastname: McArdle
authors.forename: Susan V
authors.initials: SV
authors.lastname: Brooks
authors.forename: Holly
authors.initials: H
authors.lastname: Van Remmen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015227:Lipid Peroxidation / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009119:Muscle Contraction / Q000235:genetics / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology* / Q000648:ultrastructure; D009133:Muscular Atrophy / Q000201:enzymology* / Q000235:genetics; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: C002744:3-nitrotyrosine; D014443:Tyrosine; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: central nuclei; oxidative stress; regeneration