Abstract
The Cdc25 family of protein phosphatases positively regulate the cell division cycle by activating cyclin-dependent 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 thatCdc25C−/− mice are viable and do not display any obvious abnormalities. Among adult tissues in whichCdc25C is detected, its transcripts are most abundant in testis, followed by thymus, ovary, spleen, and intestine. Mice lackingCdc25C were fertile, indicating that Cdc25Cdoes 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, andCdc25C−/− 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 thatCdc25A and/or Cdc25B may compensate for loss ofCdc25C in the mouse.
ACKNOWLEDGMENTS
We thank Peter Donovan for providing peptide antibody specific for mCdc25C. We thank the Siteman Cancer Center ES stem cell core for electroporation of the targeting construct into RW4 cells and Mike White for the blastocyst injections. We thank B. Sleckman and A. Chan for helpful suggestions and comments. We thank Y. Zhao and L. He for technical support.
This work was supported in part by a scholarship from the Lucille P. Markey foundation to J.H. M.-S.C. is an Associate and H.P.-W. is an Investigator of the Howard Hughes Medical Institute.