Hindlimb motor neurons require Cu/Zn superoxide dismutase for maintenance of neuromuscular junctions.

ABSTRACT

The role of oxidative damage in neurodegenerative disease was investigated in mice lacking cytoplasmic Cu/Zn superoxide dismutase (SOD), created by deletion of the SOD1 gene (SOD1(-/-)). SOD1(-/-) mice developed a chronic peripheral hindlimb axonopathy. Mild denervation of muscle was detected at 2 months, and behavioral and physiological motor deficits were present at 5-7 months of age. Ventral root axons were shrunken but were normal in number. The somatosensory system in SOD1(-/-) mice was mildly affected. SOD1(-/-) mice expressing Cu/Zn SOD only in brain and spinal cord were generated using transgenic mice expressing mouse SOD1 driven by the neuron-specific synapsin promoter. Neuron-specific expression of Cu/Zn SOD in SOD1(-/-) mice rescued motor neurons from the neuropathy. Therefore, Cu/Zn SOD is not required for normal motor neuron survival, but is necessary for the maintenance of normal neuromuscular junctions by hindlimb motor neurons.