PMID- 11171393 OWN - NLM STAT- MEDLINE DCOM- 20010412 LR - 20220215 IS - 0950-1991 (Print) IS - 0950-1991 (Linking) VI - 128 IP - 5 DP - 2001 Mar TI - RXR-alpha ablation in skin keratinocytes results in alopecia and epidermal alterations. PG - 675-88 AB - 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. FAU - Li, M AU - Li M AD - Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/ULP, College de France, BP 163, 67404 Illkirch Cedex, France. FAU - Chiba, H AU - Chiba H FAU - Warot, X AU - Warot X FAU - Messaddeq, N AU - Messaddeq N FAU - Gerard, C AU - Gerard C FAU - Chambon, P AU - Chambon P FAU - Metzger, D AU - Metzger D LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Development JT - Development (Cambridge, England) JID - 8701744 RN - 0 (Receptors, Retinoic Acid) RN - 0 (Retinoid X Receptors) RN - 0 (Transcription Factors) RN - 0 (Viral Proteins) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - 68238-35-7 (Keratins) RN - 9007-49-2 (DNA) RN - EC 2.7.7.- (Cre recombinase) RN - EC 2.7.7.- (Integrases) RN - EC 3.2.1.23 (beta-Galactosidase) SB - IM MH - Alopecia/genetics/pathology MH - Animals MH - Blotting, Southern MH - Cell Differentiation MH - Cloning, Molecular MH - Cysts/pathology MH - DNA/genetics/metabolism MH - Epidermis/*anatomy & histology/growth & development/immunology/ultrastructure MH - Female MH - Genes, Reporter MH - Hair Follicle/growth & development/ultrastructure MH - Immunohistochemistry MH - Integrases/genetics/metabolism MH - Intercellular Adhesion Molecule-1/metabolism MH - Keratinocytes/*cytology/metabolism MH - Keratins/*metabolism MH - Male MH - Mice MH - Mice, Inbred Strains MH - Mice, Transgenic MH - Plasmids MH - Receptors, Retinoic Acid/genetics/*metabolism MH - Recombination, Genetic MH - Retinoid X Receptors MH - T-Lymphocyte Subsets/metabolism MH - Transcription Factors/genetics/*metabolism MH - Transgenes MH - *Viral Proteins MH - beta-Galactosidase/metabolism EDAT- 2001/02/15 11:00 MHDA- 2001/04/17 10:01 CRDT- 2001/02/15 11:00 PHST- 2001/02/15 11:00 [pubmed] PHST- 2001/04/17 10:01 [medline] PHST- 2001/02/15 11:00 [entrez] AID - 10.1242/dev.128.5.675 [doi] PST - ppublish SO - Development. 2001 Mar;128(5):675-88. doi: 10.1242/dev.128.5.675.