Characteristics of spontaneous mutations in mouse germ cells

小鼠生殖细胞自发突变的特征

• 批准号: 13839004
• 负责人: ONO Tetsuya
• 金额: $ 2.3万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13839004/
• 关键词: mouse; testis; germ-line cells; mutation; mismatch repair; deletion; 自然突然変異; 減数分裂; 精原細胞; 精細胞

In an attempt to elucidate if the spontaneous mutations occurring in germ cells are different from those in somatic tissues, we have analysed spontaneous mutant frequencies in testicular cells at infant and adult stages of lacZ-transgenic mice. The infant's testis is rich with spermatogonia, while adult's testis include all kinds of cells in spermatogesis. We have also analysed molecular nature of mutations by analyzing DNA sequence of mutants.The mutant frequencies of testicular cells were similar to those in somatic tissues spch as brain and liver at both infant and adult stages. A comparison of the molecular nature of mutations between testicular cells and somatic cells, however, revealed that the frequency of deletion mutations which had direct repeat sequences at the break points and thus assumed to be originated from slippage of DNA polymerase, was lower in germ line cells than in somatic tissues. Since this kind of mutation are assumed to be suppressed, at least in part, by mismatch repair system, we analysed mutations in mismatch repair deficient mice. The frequencies of mutant appearance as well as slippage-type mutations were found to be elevated in the mice.These results suggest an important role of mismatch repair system in suppressing the occurrence of spontaneous mutation in germ line cells.

为了阐明生殖细胞中发生的自发突变是否与体细胞组织中的突变不同，我们已经分析了在睾丸细胞和LACZ-转基因小鼠的睾丸细胞和成人阶段的自发突变频率。婴儿的睾丸富含精子，而成人睾丸在精子中包括各种细胞。我们还通过分析突变体的DNA序列来分析突变的分子性质。睾丸细胞的突变频率与婴儿和成人阶段的脑和肝脏中的体细胞SPCH中的突变频率相似。然而，对睾丸细胞和体细胞之间突变的分子性质的比较表明，在断裂点处有直接重复序列并因此假定起源于DNA聚合酶的滑移的频率在生殖细胞中比在体细胞组织中低。由于认为这种突变被认为至少部分通过错配修复系统被抑制，因此我们分析了缺乏小鼠的不匹配修复中的突变。在小鼠中发现突变外观的频率以及滑移型突变升高。这些结果表明，错配修复系统在抑制生殖线细胞中自发突变的发生中的重要作用。

项目成果

Tetsuya Ono, Yoshihiko Uehara, Yusuke Saito, Hironobu Ikehata: "Mutation theory of aging, assessed in tratisgenic mice and knockout mice"Mechanisms of Ageing and Development. 123(12). 1543-1552 (2002)

Tetsuya Ono、Yoshihiko Uehara、Yusuke Saito、Hironobu Ikehata：“衰老突变理论，在遗传小鼠和基因敲除小鼠中进行评估”衰老与发育机制。

Tetsuya Ono, Hironobu Ikehata: "Mutation theory of aging, assessed in transgenic mice and knockout mice"Mechanisms of Ageing and Development. 123. 1543-1552 (2002)

Tetsuya Ono、Hironobu Ikehata：“在转基因小鼠和基因敲除小鼠中评估的衰老突变理论”衰老与发育机制。

Tetsuya Ono: "Mutation theory of aging, assessed in transgenic mice and knockout mice"Mechanisms of Ageing and Development. 123. 1543-1552 (2002)

Tetsuya Ono：“衰老突变理论，在转基因小鼠和基因敲除小鼠中进行评估”衰老与发育机制。