Genetically decreased spinal cord copper concentration prolongs life in a transgenic mouse model of amyotrophic lateral sclerosis

Mahmoud Kiaei, Ashley I. Bush, Brett M. Morrison, John Morrison, Robert A. Cherny, Irene Volitakis, M. Flint Beal, Jon W. Gordon

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Mutations in the Cu/Zn superoxide dismutase (SOD1) gene cause familial amyotrophic lateral sclerosis (FALS) by gain of an aberrant function that is not yet well understood. The role of Cu2+ in mediating the toxicity of mutant SOD1 has been earnestly contested. We tested the in vivo effects of genetically induced copper deprivation on the ALS phenotype of transgenic mice expressing G86R mutant mouse SOD1, a protein that fails to incorporate Cu 2+ in its active site. Genetically copper-deficient SOD1 G86R transgenic mice were produced by mating SOD1G86R males to female carriers of the X-linked mottled/brindled (Mobr) mutation. We found that the Mobr allele causes a severe (∼60%) depletion of spinal cord copper levels; however, despite the burden of double genetic lesions, it lengthens the lives of SOD1G86R transgenic mice by 9%. These findings provide evidence supporting a role for copper in the pathogenesis of FALS linked to SOD1 mutations.

Original languageEnglish (US)
Pages (from-to)7945-7950
Number of pages6
JournalJournal of Neuroscience
Volume24
Issue number36
DOIs
StatePublished - Sep 8 2004
Externally publishedYes

Fingerprint

Amyotrophic Lateral Sclerosis
Transgenic Mice
Copper
Spinal Cord
Mutation
Catalytic Domain
Alleles
Phenotype
Genes
Superoxide Dismutase-1
Amyotrophic lateral sclerosis 1

Keywords

  • Amyotrophic lateral sclerosis
  • Copper
  • Motor neuron
  • Mottled/brindled
  • Neurodegeneration
  • Superoxide dismutase

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Genetically decreased spinal cord copper concentration prolongs life in a transgenic mouse model of amyotrophic lateral sclerosis. / Kiaei, Mahmoud; Bush, Ashley I.; Morrison, Brett M.; Morrison, John; Cherny, Robert A.; Volitakis, Irene; Beal, M. Flint; Gordon, Jon W.

In: Journal of Neuroscience, Vol. 24, No. 36, 08.09.2004, p. 7945-7950.

Research output: Contribution to journalArticle

Kiaei, Mahmoud ; Bush, Ashley I. ; Morrison, Brett M. ; Morrison, John ; Cherny, Robert A. ; Volitakis, Irene ; Beal, M. Flint ; Gordon, Jon W. / Genetically decreased spinal cord copper concentration prolongs life in a transgenic mouse model of amyotrophic lateral sclerosis. In: Journal of Neuroscience. 2004 ; Vol. 24, No. 36. pp. 7945-7950.
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