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

Patrick A M Jansen, Ellen H van den Bogaard, 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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6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)889-891
Number of pages3
JournalExperimental Dermatology
Volume21
Issue number11
DOIs
Publication statusPublished - Nov 2012
Externally publishedYes

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    Jansen, P. A. M., van den Bogaard, E. H., Kersten, F. F. J., Oostendorp, C., van Vlijmen-Willems, I. M. J. J., Oji, V., Traupe, H., Hennies, H. C., Schalkwijk, J., & Zeeuwen, P. L. J. M. (2012). Cystatin M/E knockdown by lentiviral delivery of shRNA impairs epidermal morphogenesis of human skin equivalents. Experimental Dermatology, 21(11), 889-891. https://doi.org/10.1111/exd.12022