Document Type
Article
Publication Date
12-31-2007
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 gammadelta+ 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.
Recommended Citation
Sevilla, Lisa M; Nachat, Rachida; Groot, Karen R; Klement, John F; Uitto, Jouni; Djian, Philippe; Määttä, Arto; and Watt, Fiona M, "Mice deficient in involucrin, envoplakin, and periplakin have a defective epidermal barrier." (2007). Department of Dermatology and Cutaneous Biology Faculty Papers. Paper 21.
https://jdc.jefferson.edu/dcbfp/21
PubMed ID
18166659
Comments
This article has been peer reviewed. It was published in: The Journal of cell biology.
Volume 179, Issue 7, December 2007, Pages 1599-612.
The published version is available at DOI: 10.1083/jcb.200706187. Copyright © Rockefeller University.