| First Author | Xu J | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 4 | Pages | e18763 |
| PubMed ID | 21494564 | Mgi Jnum | J:172224 |
| Mgi Id | MGI:5005015 | Doi | 10.1371/journal.pone.0018763 |
| Citation | Xu J, et al. (2011) Separase phosphosite mutation leads to genome instability and primordial germ cell depletion during oogenesis. PLoS One 6(4):e18763 |
| abstractText | To ensure equal chromosome segregation and the stability of the genome during cell division, Separase is strictly regulated primarily by Securin binding and inhibitory phosphorylation. By generating a mouse model that contained a mutation to the inhibitory phosphosite of Separase, we demonstrated that mice of both sexes are infertile. We showed that Separase deregulation leads to chromosome mis-segregation, genome instability, and eventually apoptosis of primordial germ cells (PGCs) during embryonic oogenesis. Although the PGCs of mutant male mice were completely depleted, a population of PGCs from mutant females survived Separase deregulation. The surviving PGCs completed oogenesis but produced deficient initial follicles. These results indicate a sexual dimorphism effect on PGCs from Separase deregulation, which may be correlated with a gender-specific discrepancy of Securin. Our results reveal that Separase phospho-regulation is critical for genome stability in oogenesis. Furthermore, we provided the first evidence of a pre-zygotic mitotic chromosome segregation error resulting from Separase deregulation, whose sex-specific differences may be a reason for the sexual dimorphism of aneuploidy in gametogenesis. |
