| First Author | Subramaniam JR | Year | 2002 |
| Journal | Nat Neurosci | Volume | 5 |
| Issue | 4 | Pages | 301-7 |
| PubMed ID | 11889469 | Mgi Jnum | J:75644 |
| Mgi Id | MGI:2177323 | Doi | 10.1038/nn823 |
| Citation | Subramaniam JR, et al. (2002) Mutant SOD1 causes motor neuron disease independent of copper chaperone-mediated copper loading. Nat Neurosci 5(4):301-7 |
| abstractText | 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. |
