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Updated: Jun 26, 2026
Cell Population Analyses During Skin Carcinogenesis
Published on: August 21, 2013
Skin abnormalities generated by temporally controlled RXRalpha mutations in mouse epidermis
1Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Collège de France, Illkirch.
Abstract:
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.
Insights
Retinoid X receptor alpha (RXRalpha) is crucial for skin homeostasis. Selective ablation of RXRalpha in adult mice revealed its essential roles in hair cycling, keratinocyte proliferation, and differentiation.
Area of Science:
- Dermatology
- Molecular Biology
- Genetics
Background:
- Nuclear receptors like RARs and VDR are implicated in epidermal development and homeostasis.
- These receptors often heterodimerize with RXRs to regulate gene transcription.
- Previous genetic studies on RXRs in skin have been limited by lethality and pleiotropic effects.
Purpose of the Study:
- To overcome limitations in studying RXRalpha's function in the skin.
- To investigate the specific roles of RXRalpha in adult mouse epidermis.
- To elucidate the mechanisms of RXRalpha in skin homeostasis and disease.
Main Methods:
- Development of a novel technique for spatiotemporally controlled somatic mutations in mice.
- Utilized tamoxifen-inducible Cre-ER(T) recombinases for selective ablation of RXRalpha.
- Targeted RXRalpha knockout in adult mouse keratinocytes.
Main Results:
- RXRalpha plays a critical role in regulating hair cycling.
- RXRalpha is essential for epidermal keratinocyte proliferation.
- RXRalpha is vital for keratinocyte differentiation, likely via RXR/VDR heterodimers.
Conclusions:
- RXRalpha is indispensable for maintaining skin homeostasis in adult mammals.
- Targeted genetic manipulation provides a powerful tool for studying essential genes in skin biology.
- Understanding RXRalpha's function offers potential therapeutic targets for skin disorders.
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