title: RXR-alpha ablation in skin keratinocytes results in alopecia and epidermal alterations.
abstract: RXR-alpha is the most abundant of the three retinoid X receptors (RXRs) in the epidermis. In this study, we have used Cre-mediated recombination to selectively disrupt the mouse gene for RXR-alpha in epidermal and hair follicle keratinocytes. We show that RXR-alpha is apparently dispensable for prenatal epidermal development, while it is involved in postnatal skin maturation. After the first hair pelage, mutant mice develop a progressive alopecia, histologically characterised by the destruction of hair follicle architecture and the formation of utriculi and dermal cysts in adult mice. Our results demonstrate that RXR-alpha plays a key role in anagen initiation during the hair follicle cycle. In addition, RXR-alpha ablation results in epidermal interfollicular hyperplasia with keratinocyte hyperproliferation and aberrant terminal differentiation, accompanied by an inflammatory reaction of the skin. Our data not only provide genetic evidence that RXR-alpha/VDR heterodimers play a major role in controlling hair cycling, but also suggest that additional signalling pathways mediated by RXR-alpha heterodimerised with other nuclear receptors are involved in postnatal hair follicle growth, and homeostasis of proliferation/differentiation of epidermal keratinocytes and of the skin's immune system.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Collège de France, BP 163, 67404 Illkirch Cedex, France.
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.forename: H
authors.initials: H
authors.lastname: Chiba
authors.forename: X
authors.initials: X
authors.lastname: Warot
authors.forename: N
authors.initials: N
authors.lastname: Messaddeq
authors.forename: C
authors.initials: C
authors.lastname: Gérard
authors.forename: P
authors.initials: P
authors.lastname: Chambon
authors.forename: D
authors.initials: D
authors.lastname: Metzger
mesh_terms: D000505:Alopecia / Q000235:genetics / Q000473:pathology; D000818:Animals; D015139:Blotting, Southern; D002454:Cell Differentiation; D003001:Cloning, Molecular; D003560:Cysts / Q000473:pathology; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004817:Epidermis / Q000033:anatomy & histology* / Q000254:growth & development / Q000276:immunology / Q000648:ultrastructure; D005260:Female; D017930:Genes, Reporter; D018859:Hair Follicle / Q000254:growth & development / Q000648:ultrastructure; D007150:Immunohistochemistry; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism; D007633:Keratins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D010957:Plasmids; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D011995:Recombination, Genetic; D047488:Retinoid X Receptors; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes; D014764:Viral Proteins; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014764:Viral Proteins; D018799:Intercellular Adhesion Molecule-1; D007633:Keratins; D004247:DNA; C045073:Cre recombinase; D019426:Integrases; D001616:beta-Galactosidase