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
复制标题
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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复制
发表时间:
2002
影响因子:
2.8
通讯作者:
N. Fukunishi
中科院分区:
文献类型:
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作者:
F. Yatagai;T. Kurobe;T. Nohmi;K. Masumura;T. Tsukada;H. Yamaguchi;Kiyomi Kasai;N. Fukunishi
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.
DOI:
10.1016/0027-5107(95)00055-n
发表时间:
1995
期刊:
Mutation research
影响因子:
--
作者:
Gossen,JA;Martus,HJ;Wei,JY;Vijg,J
通讯作者:
Vijg,J
DOI:
10.1016/0027-5107(94)90258-5
发表时间:
1994
期刊:
Mutation research
影响因子:
--
作者:
Winegar,RA;Lutze,LH;Hamer,JD;O'Loughlin,KG;Mirsalis,JC
通讯作者:
Mirsalis,JC