Analyses of glutathione reductase hypomorphic mice indicate a genetic knockout.
Analyses of glutathione reductase hypomorphic mice indicate a genetic knockout.
复制标题
对谷胱甘肽还原酶低效小鼠的分析表明基因敲除。
DOI：
10.1093/toxsci/kfh268
复制
发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Smith,CharlesV
中科院分区：
文献类型：
--
作者：
Rogers,LynetteK;Tamura,Toshiya;Rogers,BryanJ;Welty,StephenE;Hansen,ThomasN;Smith,CharlesV
据报道，一种小鼠(Gr1a1Neu)的组织谷胱甘肽还原酶(GR)活性显著低于对照组小鼠的相应活性(肝脏中的GR活性低于10%)。本报告描述了这些小鼠GR基因突变(S)的特征。对Neu小鼠的RT-PCR结果表明，正常的GR编码序列中有大量缺失。Southern杂交显示，该缺失涉及从内含子1到内含子5的区域。通过聚合酶链式反应和测序确定了缺失的确切断裂点。该缺失涉及基因组GR基因的10840至23627核苷酸，功能上缺失外显子2至5。此外，该缺失会导致外显子6的框架移位，并在外显子7引入终止密码子，从而阻止蛋白质其余部分的翻译。因此，Neu小鼠不能产生功能性GR蛋白，似乎是GR的基因敲除。Neu小鼠提供了活体动物模型，用来检验关于体内组织损伤的氧化机制的假说。
A strain of mice (Gr1a1Neu) that exhibited tissue glutathione reductase (GR) activities that were substantially lower (less than 10% in liver) than the corresponding activities in control mice has been reported. The present report describes characterization of the mutation(s) in the GR gene of these mice. RT-PCR of mRNA from the Neu mice indicated a substantial deletion in the normal GR coding sequence. Southern blots revealed that the deletion involved a region spanning from intron 1 through intron 5. The exact breakpoints of the deletion were characterized by PCR and sequencing through the region encompassing the deletion. The deletion involves nucleotides 10840 through 23627 of the genomic GR gene and functionally deletes exons 2 through 5. In addition, the deletion produces a frame shift in exon 6 and introduces a stop codon in exon 7 that would prevent translation of the remainder of the protein. Consequently, the Neu mice are incapable of producing a functional GR protein and appear to be genetic knockouts for GR. The Neu mice offer live animal models with which to test hypotheses regarding oxidant mechanisms of tissue injuryin vivo.