Role of the Msh2 gene in genome maintenance and development in mouse fetuses

Dongwei He, Yali Chen, Huiying Li, Maiko Furuya, Hironobu Ikehata, Yoshihiko Uehara, Jun ichiro Komura, Tak W. Mak, Tetsuya Ono

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

In an attempt to evaluate the roles of the mismatch repair gene Msh2 in genome maintenance and in development during the fetal stage, spontaneous mutations and several developmental indices were studied in Msh2-deficient lacZ-transgenic mouse fetuses. Mutation levels in fetuses were elevated at 9.5dpc (days post coitum) when compared to wild-type mice, and the level of mutations continued to increase until the fetuses reached the newborn stage. The mutation levels in 4 different tissues of newborns showed similar magnitudes to those in the whole body. The levels remained similar after birth until 6 months of age. The molecular nature of the mutations examined in 12.5dpc fetuses of Msh2+/+ and Msh2-/- revealed unique spectra which reflect errors produced during the DNA replication process, and those corrected by a mismatch repair system. Most base substitutions and simple deletions were reduced by the presence of the Msh2 gene, whereas G:C to A:T changes at CpG sequences were not affected, suggesting that the latter change was not influenced by mismatch repair. On the other hand, analysis of developmental indices revealed that there was very little effect, including the presence of malformations, resulting from Msh2-deficiencies. These results indicate that elevated mutation levels have little effect on the development of the fetus, even if a mutator phenotype appears at the organogenesis stage.

Original languageEnglish
Pages (from-to)50-55
Number of pages6
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume734
Issue number1-2
DOIs
Publication statusPublished - 2012 Jun 1

Keywords

  • DNA mismatch repair
  • Developmental abnormality
  • LacZ
  • Mouse fetus
  • Msh2
  • Mutator phenotype

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis

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