Conditional Tek promoter-driven deletion of arginyltransferase in the germ line causes defects in gametogenesis and early embryonic lethality in mice.
Conditional Tek promoter-driven deletion of arginyltransferase in the germ line causes defects in gametogenesis and early embryonic lethality in mice.
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DOI：
10.1371/journal.pone.0007734
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发表时间：
2009-11-05
期刊：
影响因子：
3.7
通讯作者：
Kashina A
中科院分区：
文献类型：
--
作者：
Leu NA;Kurosaka S;Kashina A
Ate1 介导的翻译后蛋白精氨酰化对于心血管发育、肌动蛋白细胞骨架功能和细胞迁移至关重要。 Ate1 在细胞骨架的调节中发挥作用，对于心血管发育和血管生成（由内皮细胞的组织内迁移驱动的毛细血管重塑）至关重要。为了解决 Ate1 在发育过程中细胞骨架依赖性过程和内皮细胞功能中的作用，我们产生了条件性小鼠基因敲除，其中 Ate1 缺失由在内皮和生殖系中表达的 Tek 内皮受体酪氨酸激酶启动子驱动。与预期相反，Tek-Ate1 小鼠具有存活能力，并且没有可见的血管生成相关表型；然而，这些小鼠表现出生殖缺陷，在第二代中胚胎致死率很高，其阶段比完全 Ate1 敲除品系早得多。虽然一些早期致死率源自带有纯合 Tek-Cre 转基因的胚胎亚群（这一问题此前尚未在该商业小鼠品系中报道过），但一个独特的胚胎亚群在植入后早期阶段就具有致死性，这只能用减数分裂前生殖细胞中 Tek 驱动的 Ate1 缺失所导致的配子发生过程中先前未知的缺陷来解释。这些结果证明了 Ate1 在生殖细胞发育中的新作用。
Posttranslational protein arginylation mediated by Ate1 is essential for cardiovascular development, actin cytoskeleton functioning, and cell migration. Ate1 plays a role in the regulation of cytoskeleton and is essential for cardiovascular development and angiogenesis—capillary remodeling driven by in-tissue migration of endothelial cells. To address the role of Ate1 in cytoskeleton-dependent processes and endothelial cell function during development, we produced a conditional mouse knockout with Ate1 deletion driven by Tek endothelial receptor tyrosine kinase promoter expressed in the endothelium and in the germ line. Contrary to expectations, Tek-Ate1 mice were viable and had no visible angiogenesis-related phenotypes; however, these mice showed reproductive defects, with high rates of embryonic lethality in the second generation, at stages much earlier than the complete Ate1 knockout strain. While some of the early lethality originated from the subpopulation of embryos with homozygous Tek-Cre transgene—a problem that has not previously been reported for this commercial mouse strain—a distinct subpopulation of embryos had lethality at early post-implantation stages that could be explained only by a previously unknown defect in gametogenesis originating from Tek-driven Ate1 deletion in premeiotic germs cells. These results demonstrate a novel role of Ate1 in germ cell development.
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影响因子：
4.6
作者：
de Lange, Willem J.;Halabi, Carmen M.;Sigmund, Curt D.
通讯作者：
Sigmund, Curt D.
影响因子：
10.5
作者：
Boiani, M;Eckardt, S;McLaughlin, KJ
通讯作者：
McLaughlin, KJ
DOI：
10.1242/dev.022723
发表时间：
2008-12
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Rai R;Wong CC;Xu T;Leu NA;Dong DW;Guo C;McLaughlin KJ;Yates JR 3rd;Kashina A
通讯作者：
Kashina A
影响因子：
7.7
作者：
Rai, Reena;Mushegian, Arcady;Kashina, Anna
通讯作者：
Kashina, Anna
DOI：
10.1073/pnas.0504500102
发表时间：
2005-07-19
影响因子：
11.1
作者：
Rai, R;Kashina, A
通讯作者：
Kashina, A