Phylogenetic profiling and gene expression studies implicate a primary role of PSORS1C2 in terminal differentiation of keratinocytes. Issue 4 (16th February 2017)

• Record Type: Journal Article
• Authors: Abbas Zadeh, Salman; Mlitz, Veronika; Lachner, Julia; Golabi, Bahar; Mildner, Michael; Pammer, Johannes; Tschachler, Erwin; Eckhart, Leopold
• Other Names: Ståhle Mona guestEditor.; Schön Michael P. guestEditor.
• Is Part Of: Experimental dermatology. Volume 26:Issue 4(2017)
• Page Start: 352
• Page End: 358
• Publication Date: 2017-02-16
• Subjects: corneodesmosin -- cornification -- epidermis -- evolution -- psoriasis; Dermatology -- Periodicals; 616.5
• DOI: 10.1111/exd.13272
• Languages: English
• ISSNs: 0906-6705

Abstract

Abstract: PSORS1C2 is a gene located between coiled‐coil alpha‐helical rod protein 1 ( CCHCR1 ) and corneodesmosin ( CDSN ) within the psoriasis susceptibility locus 1 ( PSORS1 ). Here, we performed a comparative genomics analysis of the as‐yet incompletely characterized PSORS1C2 gene and determined its expression pattern in human tissues. In contrast to CCHCR1, which is common to all vertebrates investigated, PSORS1C2 and CDSN are present exclusively in mammals, indicating that the latter genes have originated after the evolutionary divergence of mammals and reptiles. CDSN is conserved in aquatic mammals, whereas PSORS1C2 orthologs contain gene‐inactivating frame shift mutations in whales and dolphins, in which the epidermal differentiation programme has degenerated. Reverse‐transcription PCR screening demonstrated that, in human tissues, PSORS1C2 is expressed principally in the epidermis and weakly in the thymus. PSORS1C2 mRNA was strongly upregulated during terminal differentiation of human keratinocytes in vitro. Immunohistochemistry revealed exclusive expression of PSORS1C2 in the granular layer of the epidermis and in cornifying epithelial cells of Hassall's corpuscles of the thymus. In summary, our results identify PSORS1C2 as a keratinocyte cornification‐associated protein that has originated in evolutionarily basal mammals and has undergone gene inactivation in association with the loss of the skin barrier function in aquatic mammals.