Knocking out the regulatory beta subunit of protein kinase CK2 in mice: Gene dosage effects in ES cells and embryos |
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Authors: | Olivier Blond Hans H Jensen Thierry Buchou Claude Cochet Olaf-Georg Issinger Brigitte Boldyreff |
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Institution: | (1) DRDC/TS-INSERM EMI0104, CEA Grenoble, Grenoble, France;(2) Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark;(3) KinaseDetect ApS, Odense, Denmark;(4) KinaseDetect ApS, Stationsvej 80, DK-5792 Aarslev, Denmark |
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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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Keywords: | CK2β embryonic lethality knockout mouse protein kinase CK2 |
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