Cystatin M/E knockdown by lentiviral delivery of shRNA impairs epidermal morphogenesis of human skin equivalents |
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| Authors: | Ferry F. J. Kersten Corien Oostendorp Ivonne M. J. J. van Vlijmen‐Willems Vinzenz Oji Heiko Traupe Hans C. Hennies Joost Schalkwijk Patrick L. J. M. Zeeuwen |
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| Affiliation: | 1. Department of Dermatology, Radboud University Nijmegen Medical Centre, , Nijmegen, the Netherlands;2. Nijmegen Centre for Molecular Life Sciences (NCMLS), , Nijmegen, the Netherlands;3. Department of Dermatology, University Hospital, , Münster, Germany;4. Cologne Center for Genomics and Cologne Cluster of Excellence on Cellular Stress Responses in Aging‐associated Diseases, University of Cologne, , Cologne, Germany;5. Division of Human Genetics, Department of Dermatology, Medical University of Innsbruck, , Innsbruck, Austria;6. Nijmegen Institute for Infection, Inflammation and Immunity (N4i), , Nijmegen, the Netherlands |
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| Abstract: | ![]()
The protease inhibitor cystatin M/E (CST6) regulates a biochemical pathway involved in stratum corneum homeostasis, and its deficiency in mice causes ichthyosis and neonatal lethality. Cystatin M/E deficiency has not been described in humans so far, and we did not detect disease‐causing mutations in the CST6 gene in a large number of patients with autosomal recessive congenital ichthyosis, who were negative for mutations in known ichthyosis‐associated genes. To investigate the phenotype of CST6 deficiency in human epidermis, we used lentiviral delivery of short hairpin RNAs that target CST6 in a 3D reconstructed skin model. Surprisingly, CST6 deficiency did not cause an ichthyosis‐like phenotype, but prevented the development of a multilayered epidermis. From this study, we conclude that CST6 deficiency may be incompatible with normal human foetal development. |
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| Keywords: | human skin equivalents ichthyosis lentivirus protease inhibitor short hairpin RNA |
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