title: Claudin-based tight junctions are crucial for the mammalian epidermal barrier: a lesson from claudin-1-deficient mice.
abstract: The tight junction (TJ) and its adhesion molecules, claudins, are responsible for the barrier function of simple epithelia, but TJs have not been thought to play an important role in the barrier function of mammalian stratified epithelia, including the epidermis. Here we generated claudin-1-deficient mice and found that the animals died within 1 d of birth with wrinkled skin. Dehydration assay and transepidermal water loss measurements revealed that in these mice the epidermal barrier was severely affected, although the layered organization of keratinocytes appeared to be normal. These unexpected findings prompted us to reexamine TJs in the epidermis of wild-type mice. Close inspection by immunofluorescence microscopy with an antioccludin monoclonal antibody, a TJ-specific marker, identified continuous TJs in the stratum granulosum, where claudin-1 and -4 were concentrated. The occurrence of TJs was also confirmed by ultrathin section EM. In claudin-1-deficient mice, claudin-1 appeared to have simply been removed from these TJs, leaving occludin-positive (and also claudin-4-positive) TJs. Interestingly, in the wild-type epidermis these occludin-positive TJs efficiently prevented the diffusion of subcutaneously injected tracer (approximately 600 D) toward the skin surface, whereas in the claudin-1-deficient epidermis the tracer appeared to pass through these TJs. These findings provide the first evidence that continuous claudin-based TJs occur in the epidermis and that these TJs are crucial for the barrier function of the mammalian skin.
authors.affiliation: Department of Cell Biology, Kyoto University Faculty of Medicine, Yoshida-Konoe, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Furuse
authors.forename: Masaki
authors.initials: M
authors.lastname: Hata
authors.forename: Kyoko
authors.initials: K
authors.lastname: Furuse
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Akinori
authors.initials: A
authors.lastname: Haratake
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Sugitani
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Noda
authors.forename: Akiharu
authors.initials: A
authors.lastname: Kubo
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Tsukita
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002463:Cell Membrane Permeability / Q000235:genetics*; D062445:Claudin-1; D004817:Epidermis / Q000002:abnormalities* / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D005804:Genes, Lethal / Q000502:physiology; D006085:Graft Survival; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D008854:Microscopy, Electron; D009154:Mutation / Q000235:genetics; D062793:Occludin; D016038:Skin Transplantation; D019108:Tight Junctions / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure
chemical_list: D062445:Claudin-1; C568113:Cldn1 protein, mouse; D008565:Membrane Proteins; D062793:Occludin; C568986:Ocln protein, mouse