Abstract
TMEM45A gene encodes an initially uncharacterized predicted transmembrane protein. We previously showed that this gene is highly expressed in keratinocytes where its expression correlates with keratinization, suggesting a role in normal epidermal physiology. To test this hypothesis, we generated TMEM45A knockout mice and found that these mice develop without any evident phenotype. The morphology of the epidermis assessed by histology and by labelling differentiation markers in immunofluorescence was not altered. Toluidine blue permeability assay showed that the epidermal barrier develops normally during embryonic development. We also showed that depletion of TMEM45A in human keratinocytes does not alter their potential to form in vitro 3D-reconstructed epidermis. Indeed, epidermis with normal morphogenesis were generated from TMEM45A-silenced keratinocytes. Their expression of differentiation markers quantified by RT-qPCR and evidenced by immunofluorescence labelling as well as their barrier function estimated by Lucifer yellow permeability were similar to the control epidermis. In summary, TMEM45A gene expression is dispensable for epidermal morphogenesis, keratinization and barrier formation. If this protein plays a role in the epidermis, its experimental depletion can possibly be compensated by other proteins in the two experimental models analyzed in this study.
Highlights
The main function of the epidermis is to maintain an efficient barrier between the organism and its external environment
We showed recently that expression of TMEM45A is strongly induced by differentiation in cultured human keratinocytes and correlates with keratinization in the granular layer of the epidermis
Mice harboring a “knockout first” conditional LacZ-tagged Tmem45a allele (Tmem45atm1a(KOMP)Mbp) were generated using a targeting vector developed by the International Mouse Phenotyping Consortium (IMPC) (Fig 1)
Summary
The main function of the epidermis is to maintain an efficient barrier between the organism and its external environment. Keratinocyte is the main cell type in the epidermis. These cells undergo proliferation and terminal differentiation, producing the cornified layer, the outermost skin barrier. This layer is composed of dead keratinocytes in which the intracellular content has been replaced by a compact keratin network, and the plasma membrane internally. TMEM45A in Epidermal Physiology reinforced by a rigid proteolipidic cornified envelope. The intercellular spaces are filled by a mostly lipidic “mortar” that participates to the impermeability of the barrier [1,2,3]. The complex process responsible for epidermal barrier maintenance is called keratinization
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