title: Targeting expression of the human vitamin D receptor to the keratinocytes of vitamin D receptor null mice prevents alopecia.
abstract: Vitamin D receptor (VDR) null mice develop hypocalcemia, hyperparathyroidism, rickets, osteomalacia and alopecia. Normalization of mineral ion homeostasis prevents all of these abnormalities except alopecia. Hair reconstitution assays, performed in athymic nude mice, demonstrate that the lack of VDR in keratinocytes leads to a defect in anagen initiation, similar to that observed in VDR null mice. Although these studies demonstrate that expression of the VDR in keratinocytes is necessary, they do not prove that it is sufficient for maintenance of the normal hair cycle. To address this hypothesis, we generated transgenic mice expressing the human VDR under the control of the keratin 14 (K14) promoter. Two highly expressing transgenic lines were mated with VDR null mice to obtain VDR null mice expressing the human VDR transgene (hVDR+/mVDR-). Expression of the transgene in the VDR null mice prevented alopecia. Furthermore, when subjected to anagen initiation, the hair follicle keratinocytes of the hVDR+/mVDR- mice demonstrated an enhanced proliferative response compared to those of control littermates. Restoration of VDR expression in the keratinocytes of VDR null mice, prevents the hair cycle defect that leads to the development of alopecia.
authors.affiliation: Endocrine Unit, Massachussetts General Hospital and Harvard Medical School, Boston MA. USA.
authors.forename: C H
authors.initials: CH
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Sakai
authors.forename: M B
authors.initials: MB
authors.lastname: Demay
mesh_terms: D000505:Alopecia / Q000517:prevention & control*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D018390:Gene Targeting; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D018167:Receptors, Calcitriol / Q000172:deficiency* / Q000235:genetics*
chemical_list: D018167:Receptors, Calcitriol