Mutant SOD1 causes motor neuron disease independent of copper chaperone-mediated copper loading

Jamuna R. Subramaniam, W. Ernest Lyons, Jian Liu, Thomas B. Bartnikas, Jeffrey Rothstein, Donald L. Price, Don W. Cleveland, Jonathan D. Gitlin, Philip C. Wong

Research output: Contribution to journalArticlepeer-review

Abstract

Copper-mediated oxidative damage is proposed to play a critical role in the pathogenesis of Cu/Zn superoxide dismutase (SOD1)-linked familial amyotrophic lateral sclerosis (FALS). We tested this hypothesis by ablating the gene encoding the copper chaperone for SOD1 (CCS) in a series of FALS-linked SOD1 mutant mice. Metabolic 64Cu labeling in SOD1-mutant mice lacking the CCS showed that the incorporation of copper into mutant SOD1 was significantly diminished in the absence of CCS. Motor neurons in CCS−/− mice showed increased rate of death after facial nerve axotomy, a response documented for SOD1−/− mice. Thus, CCS is necessary for the efficient incorporation of copper into SOD1 in motor neurons. Although the absence of CCS led to a significant reduction in the amount of copper-loaded mutant SOD1, however, it did not modify the onset and progression of motor neuron disease in SOD1-mutant mice. Hence, CCS-dependent copper loading of mutant SOD1 plays no role in the pathogenesis of motor neuron disease in these mouse models.

Original languageEnglish (US)
Pages (from-to)301-307
Number of pages7
JournalNature neuroscience
Volume5
Issue number4
DOIs
StatePublished - Apr 2002

ASJC Scopus subject areas

  • Neuroscience(all)

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