title: Deficiency of the cystine-transporter gene, xCT, does not exacerbate the deleterious phenotypic consequences of SOD1 knockout in mice.
abstract: Because glutathione scavenges reactive oxygen species (ROS) and also donates electrons to antioxidative systems, it may compensate for the oxidative stress caused by SOD1 deficiency. The cystine/glutamate transporter, which consists of two proteins, xCT and 4F2hc, has been designated system x (c) (-) . This transporter system plays a role in the maintenance of glutathione levels in mammalian cells. In the present study, we created SOD1 (-/-); xCT (-/-) double-knockout mice by intercrossing xCT-knockout and SOD1-knockout animals. We determined if the double-knockout mice express the phenotypic characteristics unique to SOD1 (-/-) mice-increased oxidative stress and the production of autoantibodies against erythrocytes. We also compared the phenotype of the double-knockout mice with those of the single-knockout and wild-type mice. Although two major antioxidative systems were found to be defective in the SOD1 (-/-); xCT (-/-) mice, relative to the SOD1 (-/-) mice, no functional deficits were observed. Based on these results, it appears that defects in system x (c) (-) do not exacerbate the phenotypic consequences of SOD1 deficiency in postnatal mice under ordinary breeding conditions.
authors.affiliation: Department of Biomolecular Function, Yamagata University, Iidanishi, Yamagata City, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Iuchi
authors.forename: Noriko
authors.initials: N
authors.lastname: Kibe
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tsunoda
authors.forename: Futoshi
authors.initials: F
authors.lastname: Okada
authors.forename: Shiro
authors.initials: S
authors.lastname: Bannai
authors.forename: Hideyo
authors.initials: H
authors.lastname: Sato
authors.forename: Junichi
authors.initials: J
authors.lastname: Fujii
mesh_terms: D027182:Amino Acid Transport System y+ / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology; D003433:Crosses, Genetic; D004912:Erythrocytes / Q000276:immunology; D027282:Fusion Regulatory Protein 1, Heavy Chain / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000502:physiology*; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
chemical_list: D027182:Amino Acid Transport System y+; D001323:Autoantibodies; D027282:Fusion Regulatory Protein 1, Heavy Chain; D017382:Reactive Oxygen Species; C492255:Slc7a11 protein, mouse; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1