Mice deficient in involucrin, envoplakin and periplakin have a defective epidermal barrier

Sevilla, LM; Nachat, R; Groot, KR; Klement, JF; Uitto, J; Djian, P; Määttä, A; Watt, FM

Abstract

The cornified envelope is assembled from transglutaminase cross-linked proteins and lipids in the outermost epidermal layers and is essential for skin barrier function. Involucrin, envoplakin, and periplakin form the protein scaffold on which the envelope assembles. To examine their combined function, we generated mice deficient in all three genes. The triple knockouts have delayed embryonic barrier formation and postnatal hyperkeratosis (abnormal accumulation of cornified cells) resulting from impaired desquamation. Cornified envelopes form but are ultrastructurally abnormal, with reduced lipid content and decreased mechanical integrity. Expression of proteases is reduced and the protease inhibitor, serpina1b, is highly upregulated, resulting in defective filaggrin processing and delayed degradation of desmoglein 1 and corneodesmosin. There is infiltration of CD4+ T cells and a reduction in resident γδ+ T cells, reminiscent of atopic dermatitis. Thus, combined loss of the cornified envelope proteins not only impairs the epidermal barrier, but also changes the composition of T cell subpopulations in the skin.

Citation

Sevilla, L., Nachat, R., Groot, K., Klement, J., Uitto, J., Djian, P., …Watt, F. (2007). Mice deficient in involucrin, envoplakin and periplakin have a defective epidermal barrier. Journal of Cell Biology, 179(7), 1599-1612. https://doi.org/10.1083/jcb.200706187

• Journal Article Type: Article
• Publication Date: Dec 1, 2007
• Deposit Date: Apr 2, 2012
• Publicly Available Date: Jun 12, 2012
• Journal: Journal of Cell Biology
• Print ISSN: 0021-9525
• Electronic ISSN: 1540-8140
• Publisher: Rockefeller University Press
• Peer Reviewed: Peer Reviewed
• Volume: 179
• Issue: 7
• Pages: 1599-1612
• DOI: https://doi.org/10.1083/jcb.200706187
• Public URL: https://durham-repository.worktribe.com/output/1501266