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.

journal_name

Exp Dermatol

journal_title

Experimental dermatology

authors

Jansen PA,van den Bogaard EH,Kersten FF,Oostendorp C,van Vlijmen-Willems IM,Oji V,Traupe H,Hennies HC,Schalkwijk J,Zeeuwen PL

doi

10.1111/exd.12022

subject

Has Abstract

pub_date

2012-11-01 00:00:00

pages

889-91

issue

11

eissn

0906-6705

issn

1600-0625

journal_volume

21

pub_type

信件
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