Disruption of the Regulatory β Subunit of Protein Kinase CK2 in Mice Leads to a Cell-Autonomous Defect and Early Embryonic Lethality

Abstract

Protein kinase CK2 is a ubiquitous protein kinase implicated in proliferation and cell survival. Its regulatory β subunit, CK2β, which is encoded by a single gene in mammals, has been suspected of regulating other protein kinases. In this work, we show that knockout of the CK2β gene in mice leads to postimplantation lethality. Mutant embryos were reduced in size at embryonic day 6.5 (E6.5). They did not exhibit signs of apoptosis but did show reduced cell proliferation. Mutant embryos were resorbed at E7.5. In vitro, CK2β^−/− morula development stopped after the blastocyst stage. Attempts to generate homozygous embryonic stem (ES) cells failed. By using a conditional knockout approach, we show that lack of CK2β is deleterious for mouse ES cells and primary embryonic fibroblasts. This is in contrast to what occurs with yeast cells, which can survive without functional CK2β. Thus, our study demonstrates that in mammals, CK2β is essential for viability at the cellular level, possibly because it acquired new functions during evolution.

ACKNOWLEDGMENTS

We thank R. Oschwald for the isolation of the CK2β genomic clone from a 129/Sv mouse genomic λ library and its characterization, H. Westphal for providing the EIIa-Cre transgenic mice, I. Marechal, S. Bama, H. Jørgensen, and M. Ritskes-Hoitinga for their efficient help with mouse breeding, and M. Thomas for critically reading the manuscript.

The project was funded by grants from the Danish Research Council (no. 21-01-0098 and 51-00-0239 to B.B.), the Ministère des Affaires Etrangères (to T.B. and B.B.), the Association pour la Recherche sur le Cancer (to M.V. and C.C.), and the INSERM, the CEA, and the Fondation pour la Recherche Médicale (to C.C.).