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

Research output: Contribution to journalLetterpeer-review

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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