8-oxoguanine causes spontaneous de novo germline mutations in mice

• DOI: 10.1038/srep04689
• Publication Date: 2014-04-15T09:13:25Z
• Authors: Mizuki Ohno; Kunihiko Sakumi; Ryutaro Fukumura; Masato Furuichi; Yuki Iwasaki; Masaaki Hokama; Toshimichi Ikemura; Teruhisa Tsuzuki; Yoichi Gondo; Yusaku Nakabeppu
• Keywords: MUTYH; Germline mosaicism; Lineage (genetic)

Abstract Spontaneous germline mutations generate genetic diversity in populations of sexually reproductive organisms and are thus regarded as a driving force evolution. However, the cause mechanism remain unclear. 8-oxoguanine (8-oxoG) is candidate molecule that causes mutations, because it makes DNA more prone to mutation constantly generated by reactive oxygen species vivo . We show here endogenous 8-oxoG caused de novo spontaneous heritable G T mice, which occurred at different stages germ cell lineage were distributed throughout chromosomes. Using exome analyses covering 40.9 Mb mouse transcribed regions, we found increased frequencies rate 2 × 10 −7 mutations/base/generation offspring Mth1/Ogg1/Mutyh triple knockout (TOY-KO) accumulate nuclear gonadal cells. The roles MTH1, OGG1 MUTYH specific for prevention 8-oxoG-induced 99% observed TOY-KO mice transversions 8-oxoG; therefore, concluded causative inheritable