RXR-alpha ablation in skin keratinocytes results in alopecia and epidermal alterations.
Fiche publication
Date publication
mars 2001
Journal
Development (Cambridge, England)
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre, Dr METZGER Daniel
Tous les auteurs :
Li M, Chiba H, Warot X, Messaddeq N, Gérard C, Chambon P, Metzger D
Lien Pubmed
Résumé
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.
Mots clés
Alopecia, genetics, Animals, Blotting, Southern, Cell Differentiation, Cloning, Molecular, Cysts, pathology, DNA, genetics, Epidermis, anatomy & histology, Female, Genes, Reporter, Hair Follicle, growth & development, Immunohistochemistry, Integrases, genetics, Intercellular Adhesion Molecule-1, metabolism, Keratinocytes, cytology, Keratins, metabolism, Male, Mice, Mice, Inbred Strains, Mice, Transgenic, Plasmids, Receptors, Retinoic Acid, genetics, Recombination, Genetic, Retinoid X Receptors, T-Lymphocyte Subsets, metabolism, Transcription Factors, genetics, Transgenes, Viral Proteins, beta-Galactosidase, metabolism
Référence
Development. 2001 Mar;128(5):675-88