RXR alpha ablation in skin keratinocytes results in alopecia and epidermalalterations

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 se lectively disrupt the mouse gene for RXR alpha in epidermal and hair follic le keratinocytes. We show that RXR alpha is apparently dispensable for pren atal epidermal development, while it is involved in postnatal skin maturati on. After the first hair pelage, mutant mice develop a progressive alopecia , histologically characterised by the destruction of hair follicle architec ture and the formation of utriculi and dermal cysts in adult mice. Our resu lts demonstrate that RXR alpha plays a key role in anagen initiation during the hair follicle cycle. In addition, RXR alpha ablation results in epider mal interfollicular hyperplasia with keratinocyte hyperproliferation and ab errant terminal differentiation, accompanied by an inflammatory reaction of the skin. Our data not only provide genetic evidence that RXR alpha /VDR h eterodimers 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 keratinocyt es and of the skin's immune system.