title: High Mutation Levels are Compatible with Normal Embryonic Development in Mlh1-Deficient Mice.
abstract: To elucidate the role of the mismatch repair gene Mlh1 in genome instability during the fetal stage, spontaneous mutations were studied in Mlh1-deficient lacZ-transgenic mouse fetuses. Mutation levels were high at 9.5 days post coitum (dpc) and gradually increased during the embryonic stage, after which they remained unchanged. In addition, mutations that were found in brain, liver, spleen, small intestine and thymus showed similar levels and no statistically significant difference was found. The molecular nature of mutations at 12.5 dpc in fetuses of Mlh1+/+and Mlh1-/-mice showed their own unique spectra, suggesting that deletion mutations were the main causes in the deficiency of the Mlh1 gene. Of note, fetuses of irradiated mice exhibited marked differences such as post-implantation loss and Mendelian distribution. Collectively, these results strongly suggest that high mutation ofMlh1-/--deficient fetuses has little effect on the fetuses during their early developmental stages, whereas Mlh1-/--deficient fetuses from X-ray irradiated mothers are clearly effected.
authors.affiliation: a   Department of Oncology and.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Fan
authors.affiliation: b   Physical Examination Center, Hebei General Hospital, Shijiazhuang, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: c   Department of Surgery, Number One Hospital of Shijiazhuang, Shijiazhuang, China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: d   Research Center and.
authors.forename: Meixiang
authors.initials: M
authors.lastname: Sang
authors.affiliation: a   Department of Oncology and.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Cai
authors.affiliation: e   Department of Clinical Bio-Cell, 4th Hospital, Hebei Medical University, Shijiazhuang, China.
authors.forename: Qiaoxia
authors.initials: Q
authors.lastname: Li
authors.affiliation: f   Laboratory of DNA Damage Signaling, Chiba Cancer Center Research Institute,Chiba, Japan; and.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Ozaki
authors.affiliation: g   Department of Cell Biology, Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ono
authors.affiliation: e   Department of Clinical Bio-Cell, 4th Hospital, Hebei Medical University, Shijiazhuang, China.
authors.forename: Dongwei
authors.initials: D
authors.lastname: He
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D053843:DNA Mismatch Repair / Q000235:genetics / Q000528:radiation effects; D047108:Embryonic Development / Q000235:genetics* / Q000528:radiation effects; D005333:Fetus / Q000196:embryology / Q000528:radiation effects; D042822:Genomic Instability / Q000235:genetics / Q000528:radiation effects; D005838:Genotype; D051379:Mice; D000070957:MutL Protein Homolog 1 / Q000172:deficiency* / Q000378:metabolism; D059645:Mutation Rate; D014965:X-Rays / Q000009:adverse effects
chemical_list: D000070957:MutL Protein Homolog 1