Tight junction dysfunction in the stratum granulosum leads to aberrant stratum corneum barrier function in claudin-1-deficient mice

Background: Tight junctions (TJs) contribute to the epithelial barrier function by preventing leakage of solutes through the intercellular space. In the skin, TJs occur in the stratum granulosum (SG), where claudin-1 and claudin-4 are expressed as adhesion molecules of TJs. Claudin-1-deficient (Cldn1(-/-)) mice die within one day of birth accompanied by excessive transepidermal water loss, indicating a critical role of TJs in the epidermal barrier function. However, it has been debated whether the impaired TJ function in the SG also affects the stratum corneum (SC) barrier function or whether it results in skin barrier defects despite a normal SC barrier. Objective: To clarify whether the impaired TJ function affects the SC barrier function in Cldn1(-/-) mice. Methods: The morphology, barrier function and biochemical characteristic of the SC were compared between Cldn1(-/-) and Cldn(+/+) mice. Results: Scanning electron microscopy demonstrated abnormally wrinkled and rough corneocytes in Cldn1(-/-) mice. Notably, the X-gal tracer easily permeated into the Cldn1(-/-) SC, and water evaporation through isolated Cidn1(-/-) SC sheets was significantly higher than that through Cldn1(+/+) SC sheets. Furthermore, the ceramide composition of the SC lipids and filaggrin processing were altered in Cldn1(-/-) mice. Conclusion: Cldn1(-/-) mice exhibited the abnormal SC formation and SC barrier defects. These findings demonstrate for the first time that TJs in the SG play crucial roles in the complete SC formation and SC barrier function. (C) 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.