Crucial Role for Mst1 and Mst2 Kinases in Early Embryonic Development of the Mouse
Crucial Role for Mst1 and Mst2 Kinases in Early Embryonic Development of the Mouse
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DOI：
10.1128/mcb.00551-09
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发表时间：
2009-12-01
影响因子：
5.3
通讯作者：
Lim, Dae-Sik
中科院分区：
文献类型：
--
作者：
Oh, Sangphil;Lee, Dongjun;Lim, Dae-Sik
哺乳动物不育 20 样激酶 1 和 2（分别为 Mst1 和 Mst2）是有效的丝氨酸/苏氨酸激酶，参与细胞增殖和细胞死亡。为了研究 Mst1 和 Mst2 的生理功能，我们生成了 Mst1 和 Mst2 突变小鼠。 Mst1(-/-) 和 Mst2(-/-) 小鼠能够存活、生育且发育正常，表明这两个基因之间可能有功能重叠。 Mst1 和 Mst2 突变小鼠的杂合和纯合组合的特征表明，含有任一基因单个拷贝的小鼠经历了正常的器官发育；然而，Mst1(-/-)；同时缺乏 Mst1 和 Mst2 基因的 Mst2(-/-) 小鼠在大约胚胎第 8.5 天开始在子宫内死亡。 Mst1(-/-); Mst2(-/-)小鼠表现出严重的生长迟缓、胎盘发育失败、卵黄囊/胚胎血管模式和原始造血功能受损、胎盘和胚胎细胞凋亡增加以及胚胎本身的增殖细胞紊乱。这些发现表明，Mst1 和 Mst2 激酶在小鼠早期发育、调节胎盘发育、血管模式、原始造血以及细胞增殖和存活中发挥着重要作用。
Mammalian sterile 20-like kinases 1 and 2 (Mst1 and Mst2, respectively) are potent serine/threonine kinases that are involved in cell proliferation and cell death. To investigate the physiological functions of Mst1 and Mst2, we generated Mst1 and Mst2 mutant mice. Mst1(-/-) and Mst2(-/-) mice were viable and fertile and developed normally, suggesting possible functional overlaps between the two genes. A characterization of heterozygous and homozygous combinations of Mst1 and Mst2 mutant mice showed that mice containing a single copy of either gene underwent normal organ development; however, Mst1(-/-); Mst2(-/-) mice lacking both Mst1 and Mst2 genes started dying in utero at approximately embryonic day 8.5. Mst1(-/-); Mst2(-/-) mice exhibited severe growth retardation, failed placental development, impaired yolk sac/embryo vascular patterning and primitive hematopoiesis, increased apoptosis in placentas and embryos, and disorganized proliferating cells in the embryo proper. These findings indicate that both Mst1 and Mst2 kinases play essential roles in early mouse development, regulating placental development, vascular patterning, primitive hematopoiesis, and cell proliferation and survival.