Disruption of the mouse protein Ser/Thr phosphatase 2Cβ gene leads to early pre-implantation lethality
Disruption of the mouse protein Ser/Thr phosphatase 2Cβ gene leads to early pre-implantation lethality
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DOI：
10.1016/j.mod.2007.04.001
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发表时间：
2007-07-01
影响因子：
2.6
通讯作者：
Tamura, Shinri
中科院分区：
文献类型：
--
作者：
Sasaki, Masato;Ohnishi, Motoko;Tamura, Shinri
蛋白磷酸酶2C β (PP2C β)是蛋白丝氨酸/苏氨酸磷酸酶（PP2C）家族的成员，该家族由至少12种不同的基因产物组成。最近的研究表明，PP2C β mRNA在成熟精子、未受精的中期卵母细胞和受精卵中积累，但在早期的2细胞和8细胞阶段，mRNA水平急剧下降，在小鼠的16细胞到囊胚阶段保持在较低水平。这些观察结果提出了PP2C β在配子体发生、受精和/或胚胎发育早期阶段起关键作用的可能性。在这项研究中，我们在小鼠身上采用基因敲除技术来测试这种可能性。我们发现PP2C β (Delta/wt)小鼠产生正常的成熟配子。然而，PP2C β (Delta/Delta)胚胎在两细胞和八细胞阶段之间死亡。我们感兴趣的是，用表达cre的质粒转染PP2C β (3lox/3lox) ES细胞产生的PP2C β (Delta/Delta) ES细胞是可存活的。此外，使用siRNA敲除PP2C β并不影响野生型ES细胞的增殖。这些观察结果表明，相对较高的PP2C β表达在植入前发育的早期阶段是特异性需要的。讨论了PP2C β (Delta/Delta)小鼠着床前早期致死的可能机制。2007爱思唯尔爱尔兰有限公司版权所有。
Protein phosphatase 2C beta (PP2C beta) is a member of a family of protein Ser/Thr phosphatases (PP2C) that is composed of at least twelve different gene products. Recent studies have revealed that PP2C beta mRNA accumulates in mature sperm, unfertilized metaphase II-arrested oocytes and zygotes, but that the mRNA level then decreases sharply between the early two-cell and eight-cell stages, remaining at low levels during the 16-cell to blastocyst stages of mice. These observations raised the possibility that PP2C beta plays a crucial role during gametogenesis, fertilization, and/or early stages of embryonic development. In this study, we employed a gene knockout technique in mice to test this possibility. We found that PP2C beta(Delta/wt) mice generate normal mature gametes. However, PP2C beta(Delta/Delta) embryos die between the two-cell and eight-cell stages. To our interest, PP2C beta(Delta/Delta) ES cells which had been generated by transfecting PP2C beta(3lox/3lox) ES cells with Cre-expressing plasmid were viable. In addition, knockdown of PP2C beta using siRNA did not affect the proliferation of wild-type ES cells. These observations suggest that relatively high PP2C beta expression is specifically required during the early stages of pre-implantation development. The possible mechanisms for the early pre-implantation lethality of PP2C beta(Delta/Delta) mice are discussed. (c) 2007 Elsevier Ireland Ltd. All rights reserved.