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Molecular and Cellular Biology, February 2003, p. 908-915, Vol. 23, No. 3
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.3.908-915.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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

Thierry Buchou,1 Muriel Vernet,2 Olivier Blond,1 Hans H. Jensen,3 Hervé Pointu,2 Birgitte B. Olsen,3 Claude Cochet,1 Olaf-Georg Issinger,3 and Brigitte Boldyreff3*

DRDC/TS-INSERM EMI0104,1 DRDC/AT, CEA Grenoble, F-38054 Grenoble, France,2 Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense M, Denmark3

Received 5 August 2002/ Returned for modification 24 September 2002/ Accepted 7 November 2002

Protein kinase CK2 is a ubiquitous protein kinase implicated in proliferation and cell survival. Its regulatory ß subunit, CK2ß, 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 CK2ß 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, CK2ß-/- 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 CK2ß 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 CK2ß. Thus, our study demonstrates that in mammals, CK2ß is essential for viability at the cellular level, possibly because it acquired new functions during evolution.

* Corresponding author. Present address: Department of Clinical Pharmacology, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany. Phone: 49 621 383 2716. Fax: 49 621 383 2024. E-mail: brigitte.boldyreff{at}kpha.ma.uni-heidelberg.de.

Molecular and Cellular Biology, February 2003, p. 908-915, Vol. 23, No. 3
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.3.908-915.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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