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

Publication ,  Journal Article
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 in: J Invest Dermatol
November 2015

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.

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Published In

J Invest Dermatol

DOI

EISSN

1523-1747

Publication Date

November 2015

Volume

135

Issue

11

Start / End Page

2603 / 2610

Location

United States

Related Subject Headings

  • Skin Absorption
  • Skin Abnormalities
  • Sensitivity and Specificity
  • Protein Precursors
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Methylation
  • Membrane Proteins
  • Immunohistochemistry
 

Citation

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Liu, K.-M., Chen, Y.-J., Shen, L.-F., Haddad, A. N. S., Song, I.-W., Chen, L.-Y., … Chen, Y.-T. (2015). Cyclic Alopecia and Abnormal Epidermal Cornification in Zdhhc13-Deficient Mice Reveal the Importance of Palmitoylation in Hair and Skin Differentiation. J Invest Dermatol, 135(11), 2603–2610. https://doi.org/10.1038/jid.2015.240
Liu, Kai-Ming, Yi-Ju Chen, Li-Fen Shen, Amir N. S. Haddad, I-Wen Song, Li-Ying Chen, Yu-Ju Chen, Jer-Yuarn Wu, Jeffrey J. Y. Yen, and Yuan-Tsong Chen. “Cyclic Alopecia and Abnormal Epidermal Cornification in Zdhhc13-Deficient Mice Reveal the Importance of Palmitoylation in Hair and Skin Differentiation.J Invest Dermatol 135, no. 11 (November 2015): 2603–10. https://doi.org/10.1038/jid.2015.240.
Liu K-M, Chen Y-J, Shen L-F, Haddad ANS, Song I-W, Chen L-Y, et al. Cyclic Alopecia and Abnormal Epidermal Cornification in Zdhhc13-Deficient Mice Reveal the Importance of Palmitoylation in Hair and Skin Differentiation. J Invest Dermatol. 2015 Nov;135(11):2603–10.
Liu, Kai-Ming, et al. “Cyclic Alopecia and Abnormal Epidermal Cornification in Zdhhc13-Deficient Mice Reveal the Importance of Palmitoylation in Hair and Skin Differentiation.J Invest Dermatol, vol. 135, no. 11, Nov. 2015, pp. 2603–10. Pubmed, doi:10.1038/jid.2015.240.
Liu K-M, Chen Y-J, Shen L-F, Haddad ANS, Song I-W, Chen L-Y, Wu J-Y, Yen JJY, Chen Y-T. Cyclic Alopecia and Abnormal Epidermal Cornification in Zdhhc13-Deficient Mice Reveal the Importance of Palmitoylation in Hair and Skin Differentiation. J Invest Dermatol. 2015 Nov;135(11):2603–2610.
Journal cover image

Published In

J Invest Dermatol

DOI

EISSN

1523-1747

Publication Date

November 2015

Volume

135

Issue

11

Start / End Page

2603 / 2610

Location

United States

Related Subject Headings

  • Skin Absorption
  • Skin Abnormalities
  • Sensitivity and Specificity
  • Protein Precursors
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Methylation
  • Membrane Proteins
  • Immunohistochemistry