title: Partial deficiency of manganese superoxide dismutase exacerbates a transgenic mouse model of amyotrophic lateral sclerosis.
abstract: The pathogenesis of neuronal cell death as a consequence of mutations in copper/zinc superoxide dismutase (SOD1) associated with familial amyotrophic lateral sclerosis may involve oxidative damage and mitochondrial dysfunction. We examined whether crossing transgenic mice with the G93A SOD1 mutation with transgenic mice with a partial depletion of manganese superoxide dismutase (SOD2) would affect the disease phenotype. Compared with G93A mice alone, the mice with partial deficiency of SOD2 and the G93A SOD1 mutation showed a significant decrease in survival and an exacerbation of motor deficits detected by rotorod testing. There was a significant exacerbation of loss of motor neurons and substantia nigra dopaminergic neurons in the G93A mice with a partial deficiency of SOD2 compared with G93A mice at 110 days. Microvesiculation of large motor neurons was more prominent in the G93A mice with a partial deficiency of SOD2 compared with G93A mice at 90 days. These findings provide further evidence that both oxidative damage and mitochondrial dysfunction may play a role in the pathogenesis of motor neuron death associated with mutations in SOD1.
authors.affiliation: Neurochemistry Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, USA.
authors.forename: O A
authors.initials: OA
authors.lastname: Andreassen
authors.forename: R J
authors.initials: RJ
authors.lastname: Ferrante
authors.forename: P
authors.initials: P
authors.lastname: Klivenyi
authors.forename: A M
authors.initials: AM
authors.lastname: Klein
authors.forename: L A
authors.initials: LA
authors.lastname: Shinobu
authors.forename: C J
authors.initials: CJ
authors.lastname: Epstein
authors.forename: M F
authors.initials: MF
authors.lastname: Beal
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000818:Animals; D000870:Anterior Horn Cells / Q000166:cytology / Q000201:enzymology; D016923:Cell Death / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000201:enzymology / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D010641:Phenotype; D017354:Point Mutation; D013378:Substantia Nigra / Q000201:enzymology / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism
chemical_list: D013482:Superoxide Dismutase