title: 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.
authors.affiliation: Department of Molecular Biology, Cephalon, Inc., West Chester, Pennsylvania, USA.
authors.forename: D G
authors.initials: DG
authors.lastname: Flood
authors.forename: A G
authors.initials: AG
authors.lastname: Reaume
authors.forename: J A
authors.initials: JA
authors.lastname: Gruner
authors.forename: E K
authors.initials: EK
authors.lastname: Hoffman
authors.forename: J D
authors.initials: JD
authors.lastname: Hirsch
authors.forename: Y G
authors.initials: YG
authors.lastname: Lin
authors.forename: K S
authors.initials: KS
authors.lastname: Dorfman
authors.forename: R W
authors.initials: RW
authors.lastname: Scott
mesh_terms: D000818:Animals; D001369:Axons / Q000201:enzymology / Q000502:physiology; D001522:Behavior, Animal; D003300:Copper / Q000502:physiology*; D046508:Culture Techniques; D004195:Disease Models, Animal; D004594:Electrophysiology; D006614:Hindlimb / Q000294:innervation*; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D009046:Motor Neurons / Q000201:enzymology* / Q000502:physiology; D009132:Muscles / Q000033:anatomy & histology / Q000378:metabolism; D009431:Neural Conduction; D009469:Neuromuscular Junction / Q000201:enzymology / Q000502:physiology*; D010477:Perfusion; D010525:Peripheral Nerves / Q000502:physiology; D011401:Promoter Regions, Genetic; D016622:Silver Staining; D013482:Superoxide Dismutase / Q000502:physiology*; D013997:Time Factors; D014018:Tissue Distribution; D015032:Zinc / Q000502:physiology*
chemical_list: D003300:Copper; D013482:Superoxide Dismutase; D015032:Zinc