Sleeping beauty transposon-based phenotypic analysis of mice:: Lack of Arpc3 results in defective trophoblast outgrowth
Sleeping beauty transposon-based phenotypic analysis of mice:: Lack of Arpc3 results in defective trophoblast outgrowth
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DOI：
10.1128/mcb.00018-06
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发表时间：
2006-08-01
影响因子：
5.3
通讯作者：
Takeda, Junji
中科院分区：
文献类型：
--
作者：
Yae, Kojiro;Keng, Vincent W.;Takeda, Junji
睡美人（SB）转座子系统已经产生了许多转座子插入突变小鼠品系，其中一些已经导致胚胎致死时，繁殖到纯合性。在这里，我们报告一个这样的插入映射到小鼠肌动蛋白相关蛋白复合物亚基3基因（Arpc 3）。Arpc 3是Arp 2/3复合物的一个组成部分，它在肌动蛋白成核中起主要作用，响应于迁移信号，从母肌动蛋白丝产生Y形分支。arpc 3转座子插入突变体只发育到囊胚阶段。体外培养的Arpc 3突变体的囊胚表现出严重的滋养层细胞的扩散障碍。在使用常规基因靶向和转座子插入等位基因产生的复合杂合子中也观察到这种表型。arpc 3缺陷突变体显示缺乏肌动蛋白丰富的结构在扩展滋养层。电子显微镜分析表明，缺乏网状结构的细胞周边，这表明在Y形分支形成的Arpc 3的作用。这些数据表明Arpc 3在Arp 2/3复合体中对滋养层生长的重要性，并表明Arpc 3可能是植入所不可或缺的。
The Sleeping Beauty (SB) transposon system has generated many transposon-insertional mutant mouse lines, some of which have resulted in embryonic lethality when bred to homozygosity. Here we report one such insertion mapped to the mouse actin-related protein complex subunit 3 gene (Arpc3). Arpc3 is a component of the Arp2/3 complex, which plays a major role in actin nucleation with Y-shaped branching from the mother actin filament in response to migration signaling. Arpc3 transposon-inserted mutants developed only to the blastocyst stage. In vitro blastocyst culture of Arpc3 mutants exhibited severe spreading impairment of trophoblasts. This phenotype was also observed in compound heterozygotes generated using conventional gene-targeted and transposon-inserted alleles. Arpc3-deficient mutants were shown to lack actin-rich structures in the spreading trophoblast. Electron microscopic analysis demonstrated the lack of mesh-like structures at the cell periphery, suggesting a role of Arpc3 in Y-shaped branching formation. These data indicate the importance of Arpc3 in the Arp2/3 complex for trophoblast outgrowth and suggest that Arpc3 may be indispensable for implantation.