title: Cyclic Alopecia and Abnormal Epidermal Cornification in Zdhhc13-Deficient Mice Reveal the Importance of Palmitoylation in Hair and Skin Differentiation.
abstract: 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.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Kai-Ming
authors.initials: KM
authors.lastname: Liu
authors.affiliation: Institute of Chemistry, Academia Sinica, Taipei, Taiwan.
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Li-Fen
authors.initials: LF
authors.lastname: Shen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Department of Biology, University of Toronto Mississauga, Mississauga, Ontario, Canada.
authors.forename: Amir N S
authors.initials: ANS
authors.lastname: Haddad
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Graduate Institute of Life Sciences, National Defence Medical Center, Taipei, Taiwan.
authors.forename: I-Wen
authors.initials: IW
authors.lastname: Song
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Taiwan Mouse Clinic, National Comprehensive Mouse Phenotyping and Drug Testing Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Chen
authors.affiliation: Institute of Chemistry, Academia Sinica, Taipei, Taiwan.
authors.forename: Yu-Ju
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Jer-Yuarn
authors.initials: JY
authors.lastname: Wu
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Jeffrey J Y
authors.initials: JJY
authors.lastname: Yen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA. Electronic address: chen0010@ibms.sinica.edu.tw.
authors.forename: Yuan-Tsong
authors.initials: YT
authors.lastname: Chen
mesh_terms: D000217:Acyltransferases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D000505:Alopecia / Q000235:genetics* / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D005786:Gene Expression Regulation; D006197:Hair / Q000254:growth & development; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011498:Protein Precursors / Q000378:metabolism; D012680:Sensitivity and Specificity; D012868:Skin Abnormalities / Q000235:genetics* / Q000473:pathology; D012869:Skin Absorption / Q000235:genetics
chemical_list: D008565:Membrane Proteins; D011498:Protein Precursors; C487794:cornifelin protein, mouse; D000217:Acyltransferases; C552301:Zdhhc13 protein, mouse