PMID- 11034212 OWN - NLM STAT- MEDLINE DCOM- 20001019 LR - 20131121 IS - 0028-0836 (Print) IS - 0028-0836 (Linking) VI - 407 IP - 6804 DP - 2000 Oct 5 TI - Skin abnormalities generated by temporally controlled RXRalpha mutations in mouse epidermis. PG - 633-6 AB - Nuclear receptors for retinoids (RARs) and vitamin D (VDR), and for some other ligands (TRs, PPARs and LXRs), maybe critical in the development and homeostasis of mammalian epidermis. It is believed that these receptors form heterodimers with retinoid X receptors (RXRs) to act as transcriptional regulators. However, most genetic approaches aimed at establishing their physiological functions in the skin have been inconclusive owing either to pleiotropic effects and redundancies between receptor isotypes in gene knockouts, or to equivocal interpretation of dominant-negative mutant studies in transgenic mice. Moreover, knockout of RXRalpha, the main skin RXR isotype, is lethal in utero before skin formation. Here we have resolved these problems by developing an efficient technique to create spatiotemporally controlled somatic mutations in the mouse. We used tamoxifen-inducible Cre-ER(T) recombinases to ablate RXRalpha selectively in adult mouse keratinocytes. We show that RXRalpha has key roles in hair cycling, probably through RXR/VDR heterodimers, and in epidermal keratinocyte proliferation and differentiation. FAU - Li, M AU - Li M AD - Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/ULP, College de France, Illkirch. FAU - Indra, A K AU - Indra AK FAU - Warot, X AU - Warot X FAU - Brocard, J AU - Brocard J FAU - Messaddeq, N AU - Messaddeq N FAU - Kato, S AU - Kato S FAU - Metzger, D AU - Metzger D FAU - Chambon, P AU - Chambon P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Nature JT - Nature JID - 0410462 RN - 0 (Receptors, Retinoic Acid) RN - 0 (Retinoid X Receptors) RN - 0 (Transcription Factors) RN - 0 (Viral Proteins) RN - 094ZI81Y45 (Tamoxifen) RN - EC 2.7.7.- (Cre recombinase) RN - EC 2.7.7.- (Integrases) SB - IM MH - Alleles MH - Alopecia/etiology/genetics/pathology MH - Animals MH - Female MH - Hair/physiology MH - Humans MH - Integrases/biosynthesis MH - Keratinocytes/physiology MH - Male MH - Mice MH - Mice, Transgenic MH - Mutagenesis MH - Receptors, Retinoic Acid/genetics/*physiology MH - Retinoid X Receptors MH - Skin Diseases/*etiology/genetics/pathology MH - *Skin Physiological Phenomena MH - Tamoxifen MH - Transcription Factors/genetics/*physiology MH - *Viral Proteins EDAT- 2000/10/18 11:00 MHDA- 2000/10/21 11:01 CRDT- 2000/10/18 11:00 PHST- 2000/10/18 11:00 [pubmed] PHST- 2000/10/21 11:01 [medline] PHST- 2000/10/18 11:00 [entrez] AID - 10.1038/35036595 [doi] PST - ppublish SO - Nature. 2000 Oct 5;407(6804):633-6. doi: 10.1038/35036595.