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

Knocking out the regulatory beta subunit of protein kinase CK2 in mice leads to early embryonic lethality. Heterozygous CK2 beta (CK2 beta(+/-)) knockout mice do not show an obvious phenotype. However, the number of heterozygous offsprings from CK2 beta(+/-) inter-crossings is lower than expected, meaning that some heterozygous embryos do not survive. Interestingly, CK2 beta(+/-) ES (Embryonic Stem) cells express a considerably lower level of CK2 beta than wild-type ES cells, whereas the level of CK2 beta in organs from heterozygous adult mice does not significantly differ from those of wild-type mice. The data suggest a compensatory mechanism that adjusts CK2 beta 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 CK2 beta(+/-) 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 CK2 beta(+/-) embryos. No correlation between CK2 beta levels in normal looking and retarded CK2 beta(+/-) embryos were found. However, a different post-translational form of CK2 beta 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 CK2 beta(+/-) cells. When ES cells were injected to induce differentiated teratocarcinoma in syngenic mice, the size of the tumours correlated with the level of CK2 beta.