Deficiency of the cystine-transporter gene, xCT, does not exacerbate the deleterious phenotypic consequences of SOD1 knockout in mice
Deficiency of the cystine-transporter gene, xCT, does not exacerbate the deleterious phenotypic consequences of SOD1 knockout in mice
复制标题
DOI：
10.1007/s11010-008-9885-3
复制
发表时间：
2008-12-01
影响因子：
4.3
通讯作者：
Fujii, Junichi
中科院分区：
文献类型：
--
作者：
Iuchi, Yoshihito;Kibe, Noriko;Fujii, Junichi
由于谷胱甘肽清除活性氧（ROS）并向抗氧化系统提供电子，它可能补偿由SOD1缺乏引起的氧化应激。胱氨酸/谷氨酸转运体由xCT和4F2hc两种蛋白组成，被命名为系统x(c)（-）。这种转运体系统在维持哺乳动物细胞中的谷胱甘肽水平中起作用。在本研究中，我们创建了SOD1(-/-)；xCT（-/-）双敲除小鼠通过xCT敲除和sod1敲除动物杂交。我们确定双敲除小鼠是否表达SOD1（-/-）小鼠特有的表型特征-氧化应激增加和红细胞自身抗体的产生。我们还比较了双基因敲除小鼠与单基因敲除小鼠和野生型小鼠的表型。虽然在SOD1-/-中发现了两个主要的抗氧化系统的缺陷；与SOD1（-/-）小鼠相比，xCT（-/-）小鼠未观察到功能缺陷。基于这些结果，在普通繁殖条件下，出生后小鼠的x(c)（-）系统缺陷似乎不会加剧SOD1缺乏的表型后果。
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.