Absence of Apparent Phenotype in Mice Lacking Cdc25C Protein Phosphatase

Abstract

The Cdc25 family of protein phosphatases positively regulate the cell division cycle by activating cyclindependent protein kinases. In humans and rodents, three Cdc25 family members denoted Cdc25A, -B, and -C have been identified. The murine forms of Cdc25 exhibit distinct patterns of expression both during development and in adult mouse tissues. In order to determine unique contributions made by the Cdc25C protein phosphatase to embryonic and adult cell cycles, mice lacking Cdc25C were generated. We report that Cdc25C ؊/؊ mice are viable and do not display any obvious abnormalities. Among adult tissues in which Cdc25C is detected, its transcripts are most abundant in testis, followed by thymus, ovary, spleen, and intestine. Mice lacking Cdc25C were fertile, indicating that Cdc25C does not contribute an essential function during spermatogenesis or oogenesis in the mouse. T-and B-cell development was also found to be normal in Cdc25C ؊/؊ mice, and Cdc25C؊/؊ mouse splenic T and B cells exhibited normal proliferative responses in vitro. Finally, the phosphorylation status of Cdc2, the timing of entry into mitosis, and the cellular response to DNA damage were unperturbed in mouse embryo fibroblasts lacking Cdc25C. These findings indicate that Cdc25A and/or Cdc25B may compensate for loss of Cdc25C in the mouse.

Repression of mRNA for the PLK cell cycle gene after DNA damage requires BRCA1

“…Most of the evidence implicating polo-like kinase in the activation of Cdc25C has evolved from work on Xenopus meiotic maturation (Kumagai and Dunphy, 1996). Still, recent data support a regulatory role of the mammalian Plk1 at the cell cycle G 2 checkpoint (Smits et al, 2000;van Vugt et al, 2001), although the finding that Cdc25c À/À mice did not display any obvious abnormalities in cellular response to DNA damage nor ability to activate Cdc2a (Chen et al, 2001) may argue against an essential function of Cdc25C in mammalian G 2 /M transition. The human Plk1 was identified on basis of its high expression levels in rapidly proliferating cells (Holtrich et al, 1994).…”

Protein kinase a modulates Cdc25B activity during meiotic resumption of mouse oocytes

“…Cdc25A and Cdc25C, although present in the oocyte, did not compensate for this function (Lincoln et al, 2002). Conversely, cdc25c Ϫ/Ϫ females are fertile, suggesting its distinct function (Chen et al, 2001). The absence of oocyte-specific conditional knockout mice for Cdc25A and the early embryonic lethality of cdc25a Ϫ/Ϫ mice preclude assessing such a role for Cdc25A (Ray et al, 2007).…”

The Plk3-Cdc25 circuit

“…It is somewhat enigmatic, however, that homozygous disruption of Cdc25C in mice yields healthy animals whose cells suffer no mitotic defect, have no alteration of Cdk1 phosphorylation and respond normally to DNA damage (Chen et al, 2001). It is possible that Cdc25A may compensate for the absence of Cdc25C in these animals since Cdc25A can bind and activate Cdk1-cyclin B, and can accelerate cell division when overexpressed (Chen et al, 2001).…”