title: Development and progression of alopecia in the vitamin D receptor null mouse.
abstract: Humans with selected mutations in the vitamin D receptor (VDR) and mouse models lacking VDR develop alopecia. Mice null for the Vdr gene are born with a normal coat of hair, but fail to initiate normal hair follicle cycling. In this study, we examined the morphology of the hair follicle of the Vdr null mouse during days 13-22 when the hair follicle normally initiates and completes the first catagen. We then explored the possibility that the abnormality in hair follicle cycling was associated with abnormal expression of hairless (Hr), a putative transcriptional regulator known to regulate hair follicle cycling and recently shown to regulate VDR transcriptional activity. Our results demonstrate the progressive deterioration of the hair follicle through catagen. Comparable to VDR, Hr was found in the basal cells of the epidermis and ORS of the hair follicle. However, Hr was also found in the IRS and matrix of the follicle, regions with little or no VDR. Hr levels increased during catagen, reaching a peak by day 19. Levels of Hr were greater in the Vdr null mice compared to wildtype controls, results confirmed by quantitative RT-PCR. We conclude that lack of VDR causes disruption of hair follicle structure during the first catagen resulting in failure of subsequent hair follicle cycling. These changes are associated with increased expression of Hr, suggesting a role for VDR in regulating Hr expression. Both Hr and VDR are required for normal hair follicle cycling.
authors.affiliation: Department of Medicine, Veterans Affairs Medical Center and University of California, San Francisco, California 94121, USA. doctor@itsa.ucsf.edu
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Bikle
authors.forename: Hashem
authors.initials: H
authors.lastname: Elalieh
authors.forename: Sandra
authors.initials: S
authors.lastname: Chang
authors.forename: Zhongjian
authors.initials: Z
authors.lastname: Xie
authors.forename: John P
authors.initials: JP
authors.lastname: Sundberg
mesh_terms: D000469:Alkaline Phosphatase / Q000032:analysis; D000505:Alopecia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D018450:Disease Progression; D004817:Epidermis / Q000737:chemistry / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics; D018859:Hair Follicle / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure; D006965:Hyperplasia; D053569:Keratin-15; D053555:Keratin-5; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D007633:Keratins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D018167:Receptors, Calcitriol / Q000032:analysis / Q000172:deficiency* / Q000235:genetics; D012867:Skin / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D053569:Keratin-15; D053555:Keratin-5; C492053:Krt15 protein, mouse; D018809:Proliferating Cell Nuclear Antigen; D018167:Receptors, Calcitriol; D014157:Transcription Factors; C088661:hr protein, mouse; D007633:Keratins; D000469:Alkaline Phosphatase