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Knocking out the regulatory beta subunit of protein kinase CK2 in mice: Gene dosage effects in ES cells and embryos

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Abstract

Knocking out the regulatory β subunit of protein kinase CK2 in mice leads to early embryonic lethality. Heterozygous CK2β (CK2β+/−) knockout mice do not show an obvious phenotype. However, the number of heterozygous offsprings from CK2β+/− inter-crossings is lower than expected, meaning that some heterozygous embryos do not survive. Interestingly, CK2β+/− ES (Embryonic Stem) cells express a considerably lower level of CK2β than wild-type ES cells, whereas the level of CK2β in organs from heterozygous adult mice does not significantly differ from those of wild-type mice. The data suggest a compensatory mechanism that adjusts CK2β levels during development in the majority of, but not in all, cases (Mol Cell Biol {23:} 908–915, 2003).

In order to find an explanation for the gene dosage effect observed for heterozygous offsprings, we analysed embryos at mid-gestation (E10.5) as well as wild-type and CK2β+/− ES cells for differences in growth rate and response to different stress agents. Analysis of E10.5 embryos generated from heterozygous matings revealed about 20% of smaller retarded CK2β+/− embryos. No correlation between CK2β levels in normal looking and retarded CK2β+/− embryos were found. However, a different post-translational form of CK2β protein has been detected in these retarded embryos. Cellular parameters such as growth rate and G1-, G2-checkpoints in ES cells were identical in both wild-type and CK2β+/− cells. When ES cells were injected to induce differentiated teratocarcinoma in syngenic mice, the size of the tumours correlated with the level of CK2β.

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Authors and Affiliations

  1. DRDC/TS-INSERM EMI0104, CEA Grenoble, Grenoble, France

    Olivier Blond, Thierry Buchou & Claude Cochet

  2. Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark

    Hans H. Jensen & Olaf-Georg Issinger

  3. KinaseDetect ApS, Odense, Denmark

    Brigitte Boldyreff

  4. KinaseDetect ApS, Stationsvej 80, DK-5792, Aarslev, Denmark

    Brigitte Boldyreff

Authors
  1. Olivier Blond
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  2. Hans H. Jensen
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  3. Thierry Buchou
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  4. Claude Cochet
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  5. Olaf-Georg Issinger
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  6. Brigitte Boldyreff
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Correspondence to Brigitte Boldyreff.

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Blond, O., Jensen, H.H., Buchou, T. et al. Knocking out the regulatory beta subunit of protein kinase CK2 in mice: Gene dosage effects in ES cells and embryos. Mol Cell Biochem 274, 31–37 (2005). https://doi.org/10.1007/s11010-005-3117-x

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  • DOI: https://doi.org/10.1007/s11010-005-3117-x

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