Claudins in the epithelium/endothelium barrier dysfucrition

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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.