Neuron-specific expression of CuZnSOD prevents the loss of muscle mass and function that occurs in homozygous CuZnSOD-knockout mice

FASEB J. 2014 Apr;28(4):1666-81. doi: 10.1096/fj.13-240390. Epub 2013 Dec 30.


Deletion of copper-zinc superoxide dismutase (CuZnSOD) in Sod1(-/-) mice leads to accelerated loss of muscle mass and force during aging, but the losses do not occur with muscle-specific deletion of CuZnSOD. To determine the role of motor neurons in the muscle decline, we generated transgenic Sod1(-/-) mice in which CuZnSOD was expressed under control of the synapsin 1 promoter (SynTgSod1(-/-) mice). SynTgSod1(-/-) mice expressed CuZnSOD in brain, spinal cord, and peripheral nerve, but not in other tissues. Sciatic nerve CuZnSOD content in SynTgSod1(-/-) mice was ~20% that of control mice, but no reduction in muscle mass or isometric force was observed in SynTgSod1(-/-) mice compared with control animals, whereas muscles of age-matched Sod1(-/-) mice displayed 30-40% reductions in mass and force. In addition, increased oxidative damage and adaptations in stress responses observed in muscles of Sod1(-/-) mice were absent in SynTgSod1(-/-) mice, and degeneration of neuromuscular junction (NMJ) structure and function occurred in Sod1(-/-) mice but not in SynTgSod1(-/-) mice. Our data demonstrate that specific CuZnSOD expression in neurons is sufficient to preserve NMJ and skeletal muscle structure and function in Sod1(-/-) mice and suggest that redox homeostasis in motor neurons plays a key role in initiating sarcopenia during aging.

Keywords: SOD1; heat-shock protein; neuromuscular junction; oxidative stress.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / genetics
  • Aging / metabolism
  • Aging / physiology
  • Animals
  • Blotting, Western
  • Electromyography
  • Humans
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Motor Neurons / metabolism*
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Muscular Atrophy / genetics
  • Muscular Atrophy / metabolism*
  • Muscular Atrophy / physiopathology
  • Neuromuscular Junction / metabolism
  • Neuromuscular Junction / physiopathology
  • Organ Size / genetics
  • Oxidation-Reduction
  • Sarcopenia / genetics
  • Sarcopenia / metabolism
  • Sarcopenia / physiopathology
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism*
  • Superoxide Dismutase-1
  • Synaptic Transmission / genetics
  • Synaptic Transmission / physiology


  • SOD1 protein, human
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1