Claudin-based tight junctions are crucial for the mammalian epidermal barrier: A lesson from claudin-1-deficient mice

Mikio Furuse, Masaki Hata, Kyoko Furuse, Yoko Yoshida, Akinori Haratake, Yoshinobu Sugitani, Tetsuo Noda, Akiharu Kubo, Shoichiro Tsukita

Research output: Contribution to journalArticle

1036 Citations (Scopus)

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 (∼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.

Original languageEnglish
Pages (from-to)1099-1111
Number of pages13
JournalJournal of Cell Biology
Volume156
Issue number6
DOIs
Publication statusPublished - 2002 Mar 18

Keywords

  • Barrier
  • Claudin-1
  • Epidermis
  • Skin
  • Tight junction

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    Furuse, M., Hata, M., Furuse, K., Yoshida, Y., Haratake, A., Sugitani, Y., Noda, T., Kubo, A., & Tsukita, S. (2002). Claudin-based tight junctions are crucial for the mammalian epidermal barrier: A lesson from claudin-1-deficient mice. Journal of Cell Biology, 156(6), 1099-1111. https://doi.org/10.1083/jcb.200110122