Cyclic Alopecia and Abnormal Epidermal Cornification in Zdhhc13-Deficient Mice Reveal the Importance of Palmitoylation in Hair and Skin Differentiation.

Published

Journal Article

Many biochemical pathways involved in hair and skin development have not been investigated. Here, we reported on the lesions and investigated the mechanism underlying hair and skin abnormalities in Zdhhc13(skc4) mice with a deficiency in DHHC13, a palmitoyl-acyl transferase encoded by Zdhhc13. Homozygous affected mice showed ragged and dilapidated cuticle of the hair shaft (CUH, a hair anchoring structure), poor hair anchoring ability, and premature hair loss at early telogen phase of the hair cycle, resulting in cyclic alopecia. Furthermore, the homozygous affected mice exhibited hyperproliferation of the epidermis, disturbed cornification, fragile cornified envelope (CE, a skin barrier structure), and impaired skin barrier function. Biochemical investigations revealed that cornifelin, which contains five palmitoylation sites at cysteine residues (C58, C59, C60, C95, and C101), was a specific substrate of DHHC13 and that it was absent in the CUH and CE structures of the affected mice. Furthermore, cornifelin levels were markedly reduced when two palmitoylated cysteines were replaced with serine (C95S and C101S). Taken together, our results suggest that DHHC13 is important for hair anchoring and skin barrier function and that cornifelin deficiency contributes to cyclic alopecia and skin abnormalities in Zdhhc13(skc4) mice.

Full Text

Duke Authors

Cited Authors

  • Liu, K-M; Chen, Y-J; Shen, L-F; Haddad, ANS; Song, I-W; Chen, L-Y; Chen, Y-J; Wu, J-Y; Yen, JJY; Chen, Y-T

Published Date

  • November 2015

Published In

Volume / Issue

  • 135 / 11

Start / End Page

  • 2603 - 2610

PubMed ID

  • 26121212

Pubmed Central ID

  • 26121212

Electronic International Standard Serial Number (EISSN)

  • 1523-1747

International Standard Serial Number (ISSN)

  • 0022-202X

Digital Object Identifier (DOI)

  • 10.1038/jid.2015.240

Language

  • eng