Genetically Decreased Spinal Cord Copper Concentration Prolongs Life in a Transgenic Mouse Model of Amyotrophic Lateral Sclerosis
書誌事項
- 公開日
- 2004-09-08
- 権利情報
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- https://creativecommons.org/licenses/by-nc-sa/4.0/
- DOI
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- 10.1523/jneurosci.2000-04.2004
- 公開者
- Society for Neuroscience
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説明
<jats:p>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 Cu<jats:sup>2+</jats:sup>in mediating the toxicity of mutant SOD1 has been earnestly contested. We tested the<jats:italic>in vivo</jats:italic>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<jats:sup>2+</jats:sup>in its active site. Genetically copper-deficient SOD1<jats:sup>G86R</jats:sup>transgenic mice were produced by mating SOD1<jats:sup>G86R</jats:sup>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 SOD1<jats:sup>G86R</jats:sup>transgenic mice by 9%. These findings provide evidence supporting a role for copper in the pathogenesis of FALS linked to SOD1 mutations.</jats:p>
収録刊行物
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- The Journal of Neuroscience
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The Journal of Neuroscience 24 (36), 7945-7950, 2004-09-08
Society for Neuroscience
