Cystatin M/E knockdown by lentiviral delivery of sh RNA impairs epidermal morphogenesis of human skin equivalents

• Published in: Experimental dermatology 2012-11, Vol.21 (11), p.889-891
• Main Authors: Jansen, Patrick A. M., van den Bogaard, Ellen H., Kersten, Ferry F. J., Oostendorp, Corien, van Vlijmen‐Willems, Ivonne M. J. J., Oji, Vinzenz, Traupe, Heiko, Hennies, Hans C., Schalkwijk, Joost, Zeeuwen, Patrick L. J. M.
• Format: Article
• Language: English
• ISSN: 0906-6705; 1600-0625
• DOI: 10.1111/exd.12022

The protease inhibitor cystatin M/E ( CST 6) 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 CST 6 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 CST 6 deficiency in human epidermis, we used lentiviral delivery of short hairpin RNA s that target CST 6 in a 3 D reconstructed skin model. Surprisingly, CST 6 deficiency did not cause an ichthyosis‐like phenotype, but prevented the development of a multilayered epidermis. From this study, we conclude that CST 6 deficiency may be incompatible with normal human foetal development.