CELL ADHESION-DEPENDENT REGULATION OF CELL GROWTH AND DIFFERENTIATION

我们敲除了两个重要的基因，闭合蛋白和膜突蛋白。ERM（ezrin/radixin/moesin）蛋白是质膜和肌动蛋白丝之间的一种普遍的交联蛋白。由于它们的表达以组织特异性方式调节，因此推测每个ERM蛋白具有独特的功能。另一方面，在细胞水平的实验表明，ERM蛋白的功能冗余。为了评估ERM蛋白在体内可能的重叠功能，通过基因打靶在胚胎干细胞中破坏位于X染色体上的膜突蛋白基因。突变的半合子雄性以及纯合子雌性小鼠完全缺乏膜突蛋白，但发育正常且可生育，在检查的所有组织中均未显示出明显的组织学异常。在突变小鼠的组织中，膜突蛋白完全消失，而不影响ezrin和radixin的表达水平和亚细胞分布。此外，在从膜突蛋白缺陷小鼠分离的血小板、成纤维细胞和肥大细胞中，膜突蛋白基因的靶向破坏不影响它们的ERM依赖性功能，即血小板聚集、成纤维细胞的应力纤维/局灶性接触形成和肥大细胞的微绒毛形成，而不补偿性上调ezrin和radixin。这些发现支持这样的观点，即ERM蛋白在细胞和全身水平上都是功能冗余的。

We knocked out two important genes, occludin and moesin. Here we summarized the results on moesin-null mice.ERM (ezrin/radixin/moesin) proteins are general cross-linkers between plasmamembranes and actin filaments. Since their expression is regulated in a tissue specific manner, unique function has been supposed for each of ERM proteins. On the other hand, experiments at the cellular level has suggested the functional redundancy of ERM proteins. To assess the possible overlapping functions of ERM proteins invivo, the moesin gene located on X chromosome was disrupted by gene targeting in embryonic stem cells. Hemizygous male as well as homozygous female mice for the mutation were completely devoid of moesin but were normally developed and fertile, showing no obvious histological abnormalities in all the tissues examined. In tissues of the mutant mice, moesin completely disappeared without affecting the expression levels and subcellular distribution of ezrin and radixin. Also in platelets, fibroblasts, and mast cells isolated from moesin-deficient mice, targeted disruption of moesin gene did not affect their ERM-dependent functions, i.e.platelet aggregation, stress fiber/focal contact formation of fibroblasts, and microvillar formation of mast cells, without compensatory up-regulation of ezrin and radixin. These findings favor the notion that ERM proteins are functionally redundant at the cellular as well as the whole body levels.