日本放射線影響学会大会講演要旨集
日本放射線影響学会第52回大会
セッションID: P1-33
会議情報

DNA修復酵素
Role of DNA mismatch repair gene Msh2 in the embryonic stage of mouse
*何 東偉小野 哲也
著者情報
キーワード: Msh2 gene, Embryo, Mutation
会議録・要旨集 フリー

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抄録
Mismatch repair (MMR) is the major pathway to improve the fidelity of DNA replication by removing mispairs from newly synthesized DNA. Especially, Msh2 gene is one of the key genes of MMR system. Studies on mice deficient in MMR genes such as Msh2, Mlh1 and Pms2 have shown that they have high levels of spontaneous mutation and high incidence of cancer indicating a close relationship between mutation and cancer. These studies, however, were done on adult mice and never examined at an earlier stage of life. Since DNA replication starts soon after fertilization, we have wondered if the spontaneous mutation increases in early life when the MMR system does not work. Here, we studied mutational burdon in Msh2-KO mice at embryonic and young stage of life. Spontaneous mutation level was judged on lacZ transgene in MutaTM mice missing Msh2 gene. They were created by mating MutaTM and Msh2(+/-) mice. Mutations in Msh2(+/-) were elevated at 9.5 days embryo and increased further till newborn age. Mutation levels in spleen and liver at 2 months of age after birth were similar to the levels at newborn stage. In brain, on the other hand, the mutation level increased continuously in the same period. These age- and tissue-dependencies could be explained by difference in gene expression level of Msh2. Preliminary study on mRNA levels by qRT-PCR seemed to support the idea. We are also examining the malformation frequencies in Msh2-deficient mice. So far, we do not observe any increase, suggesting that high level of somatic mutation might be compatible with normal embryonic development.
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© 2009 日本放射線影響学会
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