Deficiency of the cystine-transporter gene, xCT, does not exacerbate the deleterious phenotypic consequences of SOD1 knockout in mice.
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.
Iuchi
Yoshihito
Y
Department of Biomolecular Function, Yamagata University, Iidanishi, Yamagata City, Japan.
Kibe
Noriko
N
Tsunoda
Satoshi
S
Okada
Futoshi
F
Bannai
Shiro
S
Sato
Hideyo
H
Fujii
Junichi
J
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
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