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. 2002 Apr;5(4):301-7.
doi: 10.1038/nn823.

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

Jamuna R Subramaniam  1 , W Ernest Lyons, Jian Liu, Thomas B Bartnikas, Jeffrey Rothstein, Donald L Price, Don W Cleveland, Jonathan D Gitlin, Philip C Wong
Affiliations

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

Jamuna R Subramaniam et al. Nat Neurosci. 2002 Apr.

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.

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