Early development of mouse embryos null mutant for the cyclin A2 gene occurs in the absence of maternally derived cyclin A2 gene products

Progression through the mammalian cell cycle is regulated by the sequential activation and inactivation of the cyclin-dependent kinases. In adult cell s, cyclin A2-dependent kinases are required for entry into S and M phases, completion of S phase, and centrosome duplication. However, mouse embryos l acking the cyclin A2 gene nonetheless complete preimplantation development, but die soon after implantation. In this report, we investigated whether a contribution of maternal cyclin A2 mRNA and protein to early embryonic cel l cycles might explain these conflicting observations. Our data show that a maternal stock of cyclin A2 mRNA is present in the oocyte and persists aft er fertilization until the second mitotic cell cycle, when it is degraded t o undetectable levels coincident with transcriptional activation of the zyg otic genome. A portion of maternally derived cyclin A2 protein is stable du ring the first mitosis and persists in the cytoplasm, but is completely deg raded at the second mitosis. The ability of cyclin A2-null mutants to devel op normally from the four-cell to the postimplantation stage in the absence of detectable cyclin A2 gene product indicates therefore that cyclin A2 is dispensable for cellular progression during the preimplantation nongrowth period of mouse embryo development. (C) 2000 Academic Press.