Claudins in the epithelium/endothelium barrier dysfucrition

在多细胞生物中，内部环境必须与外部环境隔离和缓冲，并进一步划分为各种成分不同的流体隔间。这种划分是由描绘体表和空洞的细胞上皮片建立的。为了使上皮细胞膜起到屏障的作用，必须对细胞旁途径中的溶质扩散有一定的封闭性。脊椎动物的紧密连接(TJ)被证明是造成这种细胞间密封的原因。最近发现的Claudins，一种与TJ屏障有关的细胞黏附分子，开辟了一种新的方法来扰乱单个隔室，并在整个身体水平上评估每个隔室的生理相关性。到目前为止，已在人/鼠中鉴定出24个claudin家族成员，据报道，这些成员以不同的组合和混合比例在单个细胞层中表达。已经证明，当小鼠体内构成其所描绘的上皮细胞层TJ的主要克拉丁物种的基因被纯合敲除时，特定的隔室可以被破坏。在这个项目中，我们培育并报道了claudin-1和claudin-5偏转小鼠。Claudin-1在表皮中大量表达，Claudin-1基因缺陷的小鼠表现出严重的表皮屏障功能障碍，出生后很快脱水。脑血管内皮细胞主要表达claudin-5，在claudin-5缺陷小鼠血脑屏障受到严重影响。现在我们可以讨论Claudins与脊椎动物的区域化之间的关系。

In multicellular organisms, the internal environment must be isolated and buffered against the external environment, and further divided into various compositionally distinct fluid compartments. This compartmentalization is established by cellular sheets of epithelia delineating the body surface and cavities. For epithelial cellular sheets to function as barriers, there must be some seal to the diffusion of solutes through the paracellular pathway. Tight junctions(TJs) have teen shown to be responsible for this intercellular sealing in vertebrates. Recent identification of claudins, cell adhesion molecules responsible for the TJ barrier, opened a new way to perturb individual compartments, and to evaluate the physiological relevance of each compartment at a whole body level. To date, 24 members of the claudin family have been identified in human/mouse, and these are reported to be expressed in individual cell layers in various combinations and mixing ratios. It has been shown that a particular compartment can be destroyed, when the gene for major species of claudins constituting TJs of its delineating epithelial cell layer is homozygously knocked out in mice. In this project, we generated and reported claudin-1-and claudin-5-deflcient mice. Claudin-1 is expressed in large amounts in the epidermis, and claudin-1-deficient mice showed severe dysfunction of the epidermal barrier, being dehydrated quickly after birth. Endothelial cells of brain blood vessels primarily express claudin-5, and in claudin-5-deficient mice, the blood-brain barrier was severely affected. Now we can discuss the relationship of claudins with the compartmentalization in vertebrates.