title: Disrupted ectodermal organ morphogenesis in mice with a conditional histone deacetylase 1, 2 deletion in the epidermis.
abstract: Histone deacetylases (HDACs) are present in the epidermal layer of the skin, outer root sheath, and hair matrix. To investigate how histone acetylation affects skin morphogenesis and homeostasis, mice were generated with a K14 promoter-mediated reduction of Hdac1 or Hdac2. The skin of HDAC1 null (K14-Cre Hdac1(cKO/cKO)) mice exhibited a spectrum of lesions, including irregularly thickened interfollicular epidermis, alopecia, hair follicle dystrophy, claw dystrophy, and abnormal pigmentation. Hairs are sparse, short, and intermittently coiled. The distinct pelage hair types are lost. During the first hair cycle, hairs are lost and replaced by dystrophic hair follicles with dilated infundibulae. The dystrophic hair follicle epithelium is stratified and is positive for K14, involucrin, and TRP63, but negative for keratin 10. Some dystrophic follicles are K15 positive, but mature hair fiber keratins are absent. The digits form extra hyperpigmented claws on the lateral sides. Hyperpigmentation is observed in the interfollicular epithelium, the tail, and the feet. Hdac1 and Hdac2 dual transgenic mice (K14-Cre Hdac1(cKO/cKO) Hdac2(+/cKO)) have similar but more obvious abnormalities. These results show that suppression of epidermal HDAC activity leads to improper ectodermal organ morphogenesis and disrupted hair follicle regeneration and homeostasis, as well as indirect effects on pigmentation.
authors.affiliation: Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Hughes
authors.affiliation: Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
authors.forename: Ting-Xin
authors.initials: TX
authors.lastname: Jiang
authors.affiliation: Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
authors.forename: Sung-Jan
authors.initials: SJ
authors.lastname: Lin
authors.affiliation: Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Leung
authors.affiliation: Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kobielak
authors.affiliation: Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
authors.forename: Randall B
authors.initials: RB
authors.lastname: Widelitz
authors.affiliation: Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. Electronic address: cmchuong@usc.edu.
authors.forename: Cheng M
authors.initials: CM
authors.lastname: Chuong
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D000505:Alopecia / Q000235:genetics; D000818:Animals; D004475:Ectoderm / Q000002:abnormalities*; D004817:Epidermis / Q000002:abnormalities; D018859:Hair Follicle / Q000002:abnormalities; D056284:Histone Deacetylase 1 / Q000235:genetics*; D056464:Histone Deacetylase 2 / Q000235:genetics*; D006706:Homeostasis / Q000235:genetics; D007633:Keratins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009024:Morphogenesis / Q000235:genetics*; D009264:Nails, Malformed / Q000235:genetics / Q000473:pathology; D017384:Sequence Deletion; D012880:Skin Pigmentation / Q000235:genetics
chemical_list: D007633:Keratins; C484389:Hdac1 protein, mouse; C533424:Hdac2 protein, mouse; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2