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: Gene dosage effects in ES cells and embryos
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DOI：
10.1007/s11010-005-3117-x
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发表时间：
2005-06-01
影响因子：
4.3
通讯作者：
Boldyreff, B
中科院分区：
文献类型：
--
作者：
Blond, O;Jensen, HH;Boldyreff, B
敲除小鼠体内蛋白激酶 CK2 的调节性 β 亚基会导致早期胚胎死亡。杂合CK2β(CK2β(+/-))敲除小鼠没有表现出明显的表型。然而，CK2 beta(+/-) 杂交产生的杂合后代数量低于预期，这意味着一些杂合胚胎无法存活。有趣的是，CK2β(+/-)ES（胚胎干）细胞表达的CK2β水平明显低于野生型ES细胞，而杂合成年小鼠器官中的CK2β水平与野生型小鼠没有显着差异。数据表明，在大多数（但并非全部）情况下，在发育过程中存在调节 CK2 β 水平的补偿机制（Mol Cell Biol {23:} 908-915, 2003）。为了找到对杂合子后代观察到的基因剂量效应的解释，我们分析了妊娠中期胚胎 (E10.5) 以及野生型和 CK2 β(+/-) ES 细胞的生长速率和响应差异。不同的应激剂。对杂合交配产生的 E10.5 胚胎的分析显示，约 20% 的较小延迟 CK2 beta(+/-) 胚胎。未发现正常外观和发育迟缓的 CK2 beta(+/-) 胚胎中 CK2 beta 水平之间的相关性。然而，在这些发育迟缓的胚胎中检测到了不同的翻译后形式的 CK2 β 蛋白。 ES 细胞中的生长速率和 G1、G2 检查点等细胞参数在野生型和 CK2 beta(+/-) 细胞中是相同的。当注射 ES 细胞在同基因小鼠中诱导分化的畸胎癌时，肿瘤的大小与 CK2 β 的水平相关。
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.