Abstract 5347: DNA repair protein Rev7 is required for primordial germ cell maintenance in the mouse

Abstract

Abstract REV7 is involved in DNA repair, cell cycle regulation, gene expression and carcinogenesis. In vitro studies show that REV7 interacts with several proteins and regulates their function, and that downregulation of REV7 expression in human cancer cells results in enhancement of sensitivity to DNA damaging agents. It has been reported that human REV7 is highly expressed in the adult testis by northern blot analysis. However, the significance of REV7 in mammalian development has not been elucidated. Here, we present analyses of Rev7-deficient (Rev7-/-) mice to clarify the significance of Rev7 in mouse development. In wild-type mice (Rev7+/+), Rev7 expression was ubiquitously observed in the embryo and confined to germ cells in the testes after birth. Rev7-/- mice exhibited growth retardation and a partial embryonic lethal phenotype. Mice that survived to adulthood were infertile in both sexes and showed germ cell aplasia in the testes and ovaries. Analyses of Rev7-/- embryos revealed that primordial germ cells (PGCs) were present at embryonic day 8.5 (E8.5). However, progressive loss of PGCs was observed during migration, and PGCs were absent in the genital ridges at E13.5. An increase of apoptotic cells was detected not only among PGCs but also in the forebrain of the Rev7-/- embryo, while cell proliferation was unaffected. Gene expression analysis of E8.5 embryos showed upregulation of Oct4 and Nanog and downregulation of c-Kit and Rev3 in Rev7-/- embryos compared with those in Rev7+/- embryos. These findings indicate that Rev7 is essential for PGC maintenance by prevention of apoptotic cell death in the mouse. Note: This abstract was not presented at the meeting. Citation Format: Yoshiki Murakumo, Naoki Watanabe, Shinji Mii, Masato Asai, Naoya Asai, Kaoru Niimi, Takuya Kato, Atsushi Enomoto, Masahide Takahashi. DNA repair protein Rev7 is required for primordial germ cell maintenance in the mouse. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5347. doi:10.1158/1538-7445.AM2014-5347