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 journalLetter

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.

LanguageEnglish
Pages889-891
Number of pages3
JournalExperimental Dermatology
Volume21
Issue number11
DOIs
Publication statusPublished - Nov 2012
Externally publishedYes

Fingerprint

Cystatin M
Ichthyosis
Morphogenesis
Small Interfering RNA
Skin
Genes
Protease Inhibitors
Epidermis
Phenotype
Mutation
Human Development
Fetal Development
Cornea
Homeostasis

Cite this

Jansen, P. A. M., van den Bogaard, E. H., Kersten, F. F. J., Oostendorp, C., van Vlijmen-Willems, I. M. J. J., Oji, V., ... 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
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. / Cystatin M/E knockdown by lentiviral delivery of shRNA impairs epidermal morphogenesis of human skin equivalents. In: Experimental Dermatology. 2012 ; Vol. 21, No. 11. pp. 889-891.
@article{08ed0308f1ed4a1397c2f6db968196e5,
title = "Cystatin M/E knockdown by lentiviral delivery of shRNA impairs epidermal morphogenesis of human skin equivalents",
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.",
keywords = "Cell Proliferation, Cells, Cultured, Cystatin M, Epidermis, Gene Knockdown Techniques, Humans, Ichthyosis, Lentivirus, Models, Biological, Morphogenesis, Phenotype, RNA, Small Interfering, Skin, Artificial, Tissue Scaffolds, Letter, Research Support, Non-U.S. Gov't",
author = "Jansen, {Patrick A M} and {van den Bogaard}, {Ellen H} and Kersten, {Ferry F J} and Corien Oostendorp and {van Vlijmen-Willems}, {Ivonne M J J} and Vinzenz Oji and Heiko Traupe and Hennies, {Hans C} and Joost Schalkwijk and Zeeuwen, {Patrick L J M}",
note = "{\circledC} 2012 John Wiley & Sons A/S.",
year = "2012",
month = "11",
doi = "10.1111/exd.12022",
language = "English",
volume = "21",
pages = "889--891",
journal = "Experimental Dermatology",
issn = "0906-6705",
publisher = "Wiley-Blackwell",
number = "11",

}

Jansen, PAM, van den Bogaard, EH, Kersten, FFJ, Oostendorp, C, van Vlijmen-Willems, IMJJ, Oji, V, Traupe, H, Hennies, HC, Schalkwijk, J & Zeeuwen, PLJM 2012, 'Cystatin M/E knockdown by lentiviral delivery of shRNA impairs epidermal morphogenesis of human skin equivalents', Experimental Dermatology, vol. 21, no. 11, pp. 889-891. https://doi.org/10.1111/exd.12022

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

In: Experimental Dermatology, Vol. 21, No. 11, 11.2012, p. 889-891.

Research output: Contribution to journalLetter

TY - JOUR

T1 - Cystatin M/E knockdown by lentiviral delivery of shRNA impairs epidermal morphogenesis of human skin equivalents

AU - Jansen, Patrick A M

AU - van den Bogaard, Ellen H

AU - Kersten, Ferry F J

AU - Oostendorp, Corien

AU - van Vlijmen-Willems, Ivonne M J J

AU - Oji, Vinzenz

AU - Traupe, Heiko

AU - Hennies, Hans C

AU - Schalkwijk, Joost

AU - Zeeuwen, Patrick L J M

N1 - © 2012 John Wiley & Sons A/S.

PY - 2012/11

Y1 - 2012/11

N2 - 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.

AB - 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.

KW - Cell Proliferation

KW - Cells, Cultured

KW - Cystatin M

KW - Epidermis

KW - Gene Knockdown Techniques

KW - Humans

KW - Ichthyosis

KW - Lentivirus

KW - Models, Biological

KW - Morphogenesis

KW - Phenotype

KW - RNA, Small Interfering

KW - Skin, Artificial

KW - Tissue Scaffolds

KW - Letter

KW - Research Support, Non-U.S. Gov't

UR - http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1600-0625

U2 - 10.1111/exd.12022

DO - 10.1111/exd.12022

M3 - Letter

VL - 21

SP - 889

EP - 891

JO - Experimental Dermatology

T2 - Experimental Dermatology

JF - Experimental Dermatology

SN - 0906-6705

IS - 11

ER -

Jansen PAM, van den Bogaard EH, Kersten FFJ, Oostendorp C, van Vlijmen-Willems IMJJ, Oji V et al. Cystatin M/E knockdown by lentiviral delivery of shRNA impairs epidermal morphogenesis of human skin equivalents. Experimental Dermatology. 2012 Nov;21(11):889-891. https://doi.org/10.1111/exd.12022