An alpha-E-catenin gene trap mutation defines its function in preimplantation development
An alpha-E-catenin gene trap mutation defines its function in preimplantation development
复制标题
DOI：
10.1073/pnas.94.3.901
复制
发表时间：
1997-02-04
影响因子：
11.1
通讯作者：
Gruss, P
中科院分区：
文献类型：
--
作者：
Torres, M;Stoykova, A;Gruss, P
连环蛋白是与钙粘附素的细胞质结构域相关的蛋白质，钙粘附素是一种跨膜细胞黏附分子家族。钙粘附素-连环蛋白黏附系统参与发育过程中的形态发生和维持不同组织类型的完整性。使用基因陷阱策略，我们已经分离出编码α-E-连环蛋白基因的小鼠突变。这种形式的α-连环蛋白在上皮细胞类型中经常与E-钙粘蛋白共表达。获得的突变消除了蛋白质的羧基末端的三分之一，但仍会引起完全丧失功能的表型。纯合子突变体表现出滋养层上皮(第一个分化的胚胎组织)的破坏，因此发育受阻于胚泡阶段。这种表型与在E-钙粘蛋白突变胚胎中观察到的缺陷相似。我们的结果表明，α-E-连环蛋白的羧基末端对其功能是必需的，并为α-E-连环蛋白在体内的作用提供了证据，证实了该分子是滋养层上皮细胞中E-钙粘连蛋白的天然伙伴。
Catenins are proteins associated with the cytoplasmic domain of cadherins, a family of transmembrane cell adhesion molecules. The cadherin-catenin adhesion system is involved in morphogenesis during development and in the maintenance of the integrity of different tissue types. Using a gene trap strategy, we have isolated a mouse mutation for the gene encoding the alpha-E-catenin. This form of the alpha-catenin appears frequently coexpressed with E-cadherin in epithelial cell types. The mutation obtained eliminates the carboxyl-terminal third of the protein but nevertheless provokes a complete loss-of-function phenotype. Homozygous mutants show disruption of the trophoblast epithelium (the first differentiated embryonic tissue), and development is consequently blocked at the blastocyst stage. This phenotype parallels the defects observed in E-cadherin mutant embryos. Our results show the requirement of the alpha-E-catenin carboxy terminus for its function and represent evidence of the role of the alpha-E-catenin in vivo, identifying this molecule as the natural partner of the E-cadherin in trophoblast epithelium.