Partial deficiency of manganese superoxide dismutase exacerbates a transgenic mouse model of amyotrophic lateral sclerosis

Ole A. Andreassen, Robert J. Ferrante, P. Klivényi, Autumn M. Klein, Leslie A. Shinobu, Charles J. Epstein, M. Flint Beal

Research output: Contribution to journalArticle

65 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)447-455
Number of pages9
JournalAnnals of Neurology
Volume47
Issue number4
DOIs
Publication statusPublished - 2000

Fingerprint

Amyotrophic Lateral Sclerosis
Transgenic Mice
Superoxide Dismutase
Motor Neurons
Mutation
Dopaminergic Neurons
Substantia Nigra
Zinc
Copper
Cell Death
Phenotype

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Partial deficiency of manganese superoxide dismutase exacerbates a transgenic mouse model of amyotrophic lateral sclerosis. / Andreassen, Ole A.; Ferrante, Robert J.; Klivényi, P.; Klein, Autumn M.; Shinobu, Leslie A.; Epstein, Charles J.; Beal, M. Flint.

In: Annals of Neurology, Vol. 47, No. 4, 2000, p. 447-455.

Research output: Contribution to journalArticle

Andreassen, Ole A. ; Ferrante, Robert J. ; Klivényi, P. ; Klein, Autumn M. ; Shinobu, Leslie A. ; Epstein, Charles J. ; Beal, M. Flint. / Partial deficiency of manganese superoxide dismutase exacerbates a transgenic mouse model of amyotrophic lateral sclerosis. In: Annals of Neurology. 2000 ; Vol. 47, No. 4. pp. 447-455.
@article{5c1987f7c743465ba2c279f610336265,
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.",
author = "Andreassen, {Ole A.} and Ferrante, {Robert J.} and P. Kliv{\'e}nyi and Klein, {Autumn M.} and Shinobu, {Leslie A.} and Epstein, {Charles J.} and Beal, {M. Flint}",
year = "2000",
doi = "10.1002/1531-8249(200004)47:4<447::AID-ANA7>3.0.CO;2-R",
language = "English",
volume = "47",
pages = "447--455",
journal = "Annals of Neurology",
issn = "0364-5134",
publisher = "John Wiley and Sons Inc.",
number = "4",

}

TY - JOUR

T1 - Partial deficiency of manganese superoxide dismutase exacerbates a transgenic mouse model of amyotrophic lateral sclerosis

AU - Andreassen, Ole A.

AU - Ferrante, Robert J.

AU - Klivényi, P.

AU - Klein, Autumn M.

AU - Shinobu, Leslie A.

AU - Epstein, Charles J.

AU - Beal, M. Flint

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0034113695&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034113695&partnerID=8YFLogxK

U2 - 10.1002/1531-8249(200004)47:4<447::AID-ANA7>3.0.CO;2-R

DO - 10.1002/1531-8249(200004)47:4<447::AID-ANA7>3.0.CO;2-R

M3 - Article

C2 - 10762155

AN - SCOPUS:0034113695

VL - 47

SP - 447

EP - 455

JO - Annals of Neurology

JF - Annals of Neurology

SN - 0364-5134

IS - 4

ER -