RXRα ablation in skin keratinocytes results in alopecia and epidermal alterations

Abstract

RXRα 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 RXRα in epidermal and hair follicle keratinocytes. We show that RXRα 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 RXRα plays a key role in anagen initiation during the hair follicle cycle. In addition, RXRα 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 RXRα/VDR heterodimers play a major role in controlling hair cycling, but also suggest that additional signalling pathways mediated by RXRα 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.