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.
authors.forename: Patrick A M
authors.initials: PA
authors.lastname: Jansen
authors.forename: Ellen H
authors.initials: EH
authors.lastname: van den Bogaard
authors.forename: Ferry F J
authors.initials: FF
authors.lastname: Kersten
authors.forename: Corien
authors.initials: C
authors.lastname: Oostendorp
authors.forename: Ivonne M J J
authors.initials: IM
authors.lastname: van Vlijmen-Willems
authors.forename: Vinzenz
authors.initials: V
authors.lastname: Oji
authors.forename: Heiko
authors.initials: H
authors.lastname: Traupe
authors.forename: Hans C
authors.initials: HC
authors.lastname: Hennies
authors.forename: Joost
authors.initials: J
authors.lastname: Schalkwijk
authors.forename: Patrick L J M
authors.initials: PL
authors.lastname: Zeeuwen
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D055332:Cystatin M / Q000235:genetics* / Q000502:physiology; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000254:growth & development*; D055785:Gene Knockdown Techniques; D006801:Humans; D007057:Ichthyosis / Q000473:pathology; D016086:Lentivirus / Q000235:genetics*; D008954:Models, Biological; D009024:Morphogenesis / Q000187:drug effects / Q000235:genetics*; D010641:Phenotype; D034741:RNA, Small Interfering / Q000235:genetics* / Q000494:pharmacology; D017768:Skin, Artificial; D054457:Tissue Scaffolds
chemical_list: C525104:CST6 protein, human; D055332:Cystatin M; D034741:RNA, Small Interfering