The common neurotrophin receptor CD271, also called p75NTR, is the transmembrane low-affinity receptor for neurotrophins, belonging to the TNF superfamily. In the skin, CD271 is involved in the differentiation process and seems like to be implicated in cutaneous pathogenesis. To date, different animal models have been developed to obtain null mutations of CD271, but they defy to explain CD271 precise role in keratinocytes. By using a Keratin14-Cre mediated excision of the CD271 gene flanked by loxP sites, we generated a novel mouse model with a conditional deletion of CD271 in the epidermis. The phenotypical characterization of the CD271cKO mice was conducted at different steps of postnatal development (P1-6; P14-30; Monthly to 1 year). The analysis of the cKO vs WT skin highlighted a profound epidermis disorganization, as basal keratinocytes lose their typical palisade disposition. cKO skin epidermis appears to be significantly thicker, while dermis shows a higher amount of hair follicles than WT mice. P1 cKO skin and keratinocytes showed a higher activation of markers associated with hyperproliferation and stemness, such as a lower expression of Dlx3 and a higher level of KRT6. Starting from 4 months old, cKO mice spontaneously developed skin lesions, with characteristics resembling the hyperproliferative skin diseases, including inflammatory cell accumulation, as showed by the analysis of markers associated with differentiation and proliferation or malignancy (KRT1, Cyclin D, BCL2). Globally, these data strongly designate CD271 as a key regulator of differentiation and skin organization in healthy condition and during aging. Therefore, CD271cKO model will be a key tool for the study of the NT network in the development of various pathological processes.

ESDR186 - Dissecting the role of the common neurotrophin receptor CD271 in the skin: generation and characterization of a novel mouse model with keratinocyte-specific conditional deletion

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.