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 CK2beta (CK2beta+/-) knockout mice do not show an obvious phenotype. However, the number of heterozygous offsprings from CK2B+/- inter-crossings is lower than expected, meaning that some heterozygous embryos do not survive. Interestingly, CK2beta+/- ES (Embryonic Stem) cells express a considerably lower level of CK2beta than wild-type ES cells, whereas the level of CK2beta in organs from heterozygous adult mice does not significantly differ from those of wild-type mice. The data suggest a compensatory mechanism that adjusts CK2beta 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 CK2beta+/- 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 CK2beta+/- embryos. No correlation between CK2beta levels in normal looking and retarded CK2beta+/- embryos were found. However, a different post-translational form of CK2beta 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 CK2beta+/- cells. When ES cells were injected to induce differentiated teratocarcinoma in syngenic mice, the size of the tumours correlated with the level of CK2beta.
Blond
Olivier
O
DRDC/TS-INSERM EMI104, CEA Grenoble, Grenoble, France.
Jensen
Hans H
HH
Buchou
Thierry
T
Cochet
Claude
C
Issinger
Olaf-Georg
OG
Boldyreff
Brigitte
B
D000818:Animals; D047390:Casein Kinase II / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D004622:Embryo, Mammalian / Q000002:abnormalities* / Q000201:enzymology; D018628:Gene Dosage; D006579:Heterozygote; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000201:enzymology / Q000502:physiology*; D018243:Teratocarcinoma / Q000201:enzymology / Q000473:pathology
D021122:Protein Subunits; D047390:Casein Kinase II