Oh Sangphil, Lee Dongjun, Kim Tackhoon, Kim Tae-Shin, Oh Hyun Jung, Hwang Chae Young, Kong Young-Yun, Kwon Ki-Sun, Lim Dae-Sik
National Research Laboratory of Molecular Genetics, Department of Biological Science, KAIST, Daejeon 305-701, South Korea.
Mol Cell Biol. 2009 Dec;29(23):6309-20. doi: 10.1128/MCB.00551-09. Epub 2009 Sep 28.
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.
哺乳动物不育20样激酶1和2（分别为Mst1和Mst2）是参与细胞增殖和细胞死亡的强效丝氨酸/苏氨酸激酶。为了研究Mst1和Mst2的生理功能，我们构建了Mst1和Mst2突变小鼠。Mst1（-/-）和Mst2（-/-）小鼠存活且可育，发育正常，这表明这两个基因可能存在功能重叠。对Mst1和Mst2突变小鼠的杂合子和纯合子组合进行的表征显示，含有任一基因单拷贝的小鼠器官发育正常；然而，同时缺失Mst1和Mst2基因的Mst1（-/-）；Mst2（-/-）小鼠在胚胎期约8.5天时开始在子宫内死亡。Mst1（-/-）；Mst2（-/-）小鼠表现出严重的生长迟缓、胎盘发育失败、卵黄囊/胚胎血管模式形成受损以及原始造血功能受损、胎盘和胚胎中的细胞凋亡增加，并且胚胎本身的增殖细胞排列紊乱。这些发现表明，Mst1和Mst2激酶在小鼠早期发育中都起着至关重要的作用，调节胎盘发育、血管模式形成、原始造血以及细胞增殖和存活。
