title: Role of the Msh2 gene in genome maintenance and development in mouse fetuses.
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 9.5 dpc (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 12.5 dpc 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.
authors.affiliation: Department of Cell Biology, Graduate School of Medicine, Tohoku University, Japan.
authors.forename: Dongwei
authors.initials: D
authors.lastname: He
authors.forename: Yali
authors.initials: Y
authors.lastname: Chen
authors.forename: Huiying
authors.initials: H
authors.lastname: Li
authors.forename: Maiko
authors.initials: M
authors.lastname: Furuya
authors.forename: Hironobu
authors.initials: H
authors.lastname: Ikehata
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Uehara
authors.forename: Jun-ichiro
authors.initials: J
authors.lastname: Komura
authors.forename: Tak W
authors.initials: TW
authors.lastname: Mak
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ono
mesh_terms: D000818:Animals; D004260:DNA Repair; D004261:DNA Replication; D047109:Fetal Development / Q000235:genetics*; D005333:Fetus; D051379:Mice; D008822:Mice, Transgenic; D051718:MutS Homolog 2 Protein / Q000172:deficiency / Q000235:genetics*; D009154:Mutation; D059645:Mutation Rate; D010641:Phenotype
chemical_list: C497173:Msh2 protein, mouse; D051718:MutS Homolog 2 Protein