{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1362825896209854720.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1523/jneurosci.2000-04.2004"}},{"identifier":{"@type":"URI","@value":"https://syndication.highwire.org/content/doi/10.1523/JNEUROSCI.2000-04.2004"}}],"dc:title":[{"@value":"Genetically Decreased Spinal Cord Copper Concentration Prolongs Life in a Transgenic Mouse Model of Amyotrophic Lateral Sclerosis"}],"description":[{"type":"abstract","notation":[{"@value":"<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>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380579819859087618","@type":"Researcher","foaf:name":[{"@value":"Mahmoud Kiaei"}]},{"@id":"https://cir.nii.ac.jp/crid/1380579819859087616","@type":"Researcher","foaf:name":[{"@value":"Ashley I. Bush"}]},{"@id":"https://cir.nii.ac.jp/crid/1380579819859087619","@type":"Researcher","foaf:name":[{"@value":"Brett M. Morrison"}]},{"@id":"https://cir.nii.ac.jp/crid/1380579819859087744","@type":"Researcher","foaf:name":[{"@value":"John H. Morrison"}]},{"@id":"https://cir.nii.ac.jp/crid/1380579819859087617","@type":"Researcher","foaf:name":[{"@value":"Robert A. Cherny"}]},{"@id":"https://cir.nii.ac.jp/crid/1380579819859087620","@type":"Researcher","foaf:name":[{"@value":"Irene Volitakis"}]},{"@id":"https://cir.nii.ac.jp/crid/1380579819859087745","@type":"Researcher","foaf:name":[{"@value":"M. Flint Beal"}]},{"@id":"https://cir.nii.ac.jp/crid/1380579819859087621","@type":"Researcher","foaf:name":[{"@value":"Jon W. Gordon"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"02706474"},{"@type":"EISSN","@value":"15292401"}],"prism:publicationName":[{"@value":"The Journal of Neuroscience"}],"dc:publisher":[{"@value":"Society for Neuroscience"}],"prism:publicationDate":"2004-09-08","prism:volume":"24","prism:number":"36","prism:startingPage":"7945","prism:endingPage":"7950"},"reviewed":"false","dc:rights":["https://creativecommons.org/licenses/by-nc-sa/4.0/"],"url":[{"@id":"https://syndication.highwire.org/content/doi/10.1523/JNEUROSCI.2000-04.2004"}],"createdAt":"2004-09-08","modifiedAt":"2023-04-13","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360285707001028096","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Expression of secreted phosphoprotein 1 (osteopontin) in human sensorimotor cortex and spinal cord: Changes in patients with amyotrophic lateral sclerosis"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285707364035584","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Dysregulation of intracellular copper homeostasis is common to transgenic mice expressing human mutant superoxide dismutase-1s regardless of their copper-binding abilities"}]},{"@id":"https://cir.nii.ac.jp/crid/1360846645607752448","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Copper Homeostasis as a Therapeutic Target in Amyotrophic Lateral Sclerosis with SOD1 Mutations"}]},{"@id":"https://cir.nii.ac.jp/crid/1360848657089752576","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Monomerized Cu,Zn-superoxide dismutase induces oxidative stress through aberrant Cu binding"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1523/jneurosci.2000-04.2004"},{"@type":"CROSSREF","@value":"10.1016/j.nbd.2013.01.001_references_DOI_BmsCyGEdmNXY3399NLjIu3VEso6"},{"@type":"CROSSREF","@value":"10.1016/j.freeradbiomed.2010.01.008_references_DOI_BmsCyGEdmNXY3399NLjIu3VEso6"},{"@type":"CROSSREF","@value":"10.3390/ijms17050636_references_DOI_BmsCyGEdmNXY3399NLjIu3VEso6"},{"@type":"CROSSREF","@value":"10.1016/j.brainres.2016.10.030_references_DOI_BmsCyGEdmNXY3399NLjIu3VEso6"}]}