Heavy‐ion‐induced mutations in the gpt delta transgenic mouse: Effect of p53 gene knockout

Heavy‐ion‐induced mutations in the gpt delta transgenic mouse: Effect of p53 gene knockout
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重离子诱导的 gpt delta 转基因小鼠突变:p53 基因敲除的影响

DOI:
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发表时间:
2002
影响因子:
2.8
通讯作者:
N. Fukunishi
N. Fukunishi
中科院分区:
环境科学与生态学3区
文献类型:
--
作者:
F. Yatagai;T. Kurobe;T. Nohmi;K. Masumura;T. Tsukada;H. Yamaguchi;Kiyomi Kasai;N. Fukunishi

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通过构建新的转基因小鼠品系,即 p53 基因敲除 (p53−/−) gpt delta,研究了 p53 基因缺失对重离子诱导突变的影响。在该小鼠模型中,整合到小鼠基因组中的 lambda DNA 缺失优先选择为螺旋噬菌体,然后可以对其进行分子分析。小鼠接受 10 Gy 的全身碳离子照射。 RIKEN 环形回旋加速器将碳离子加速至 135 MeV/u。 p53缺陷显着增加了接受C离子照射的小鼠肾脏中的Spi突变频率(MF):在p53−/−和p53+/+小鼠中,照射后Spi‐MF分别比背景水平增加了4.4倍和2.8倍。 p53−/− 和 p53+/+ 小鼠之间的背景 Spi‐ MF 没有显着差异。 Spi-突变体的序列分析表明,p53-/-小鼠肾脏Spi-MF的增强主要是由于复杂或重排型缺失的增加。与肾脏相反,p53 缺陷对肝脏中的 Sp-MF 没有影响:p53−/− 和 p53+/+ 小鼠在接受照射后,Spi-MF 分别增加了 3.0 倍和 2.7 倍。我们的结果表明,p53 以器官特异性方式抑制重离子照射诱导的缺失突变。环境。摩尔。诱变剂。 40:216–225, 2002。© 2002 Wiley-Liss, Inc.
The influence of the loss of p53 gene on heavy‐ion‐induced mutations was examined by constructing a new line of transgenic mice, p53 knockout (p53−/−) gpt delta. In this mouse model, deletions in lambda DNA integrated into the mouse genome are preferentially selected as Spi‐ phages, which can then be subjected to molecular analysis. Mice were exposed to 10 Gy of whole‐body carbon‐ion irradiation. The carbon ions were accelerated to 135 MeV/u by the RIKEN Ring Cyclotron. The p53 defect markedly enhanced the Spi‐ mutant frequency (MF) in the kidneys of mice exposed to C‐ion irradiation: the Spi‐ MF increased 4.4‐ and 2.8‐fold over the background level after irradiation in p53−/− and p53+/+ mice, respectively. There was no significant difference in the background Spi‐ MF between p53−/− and p53+/+ mice. Sequence analysis of the Spi‐ mutants indicated that the enhancement of kidney Spi‐ MF in p53−/− mice was primarily due to an increase in complex or rearranged‐type deletions. In contrast to the kidney, the p53 defect had no effect on the Spi‐ MF in liver: Spi‐ MF increased 3.0‐ and 2.7‐fold after the irradiation in p53−/− and p53+/+ mice, respectively. Our results suggest that p53 suppresses deletion mutations induced by heavy‐ion irradiation in an organ‐specific manner. Environ. Mol. Mutagen. 40:216–225, 2002. © 2002 Wiley‐Liss, Inc.
基于 LacZ 质粒的转基因小鼠模型中自发和 X 射线诱导的缺失突变。
DOI: 10.1016/0027-5107(95)00055-n
发表时间: 1995
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