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.
PY - 2012
Y1 - 2012
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 neonatallethality. 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 ichthyosisassociated 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, butprevented the development of a multilayered epidermis. From this study, we conclude that CST6 deficiency may be incompatible with normal human foetal development. Abbreviations: ARCI, autosomal recessive congenital ichthyosis; CST6, cystatin M/E; CTSL, cathepsin L; CTSV, cathepsin V; IFAP, ichthyosis follicularis with atrichia and photophobia; KP, keratosis pilaris; LGMN, legumain; LI, lamellar ichthyosis; qPCR, real-time quantitative PCR; shRNA, short hairpin RNA.
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 neonatallethality. 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 ichthyosisassociated 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, butprevented the development of a multilayered epidermis. From this study, we conclude that CST6 deficiency may be incompatible with normal human foetal development. Abbreviations: ARCI, autosomal recessive congenital ichthyosis; CST6, cystatin M/E; CTSL, cathepsin L; CTSV, cathepsin V; IFAP, ichthyosis follicularis with atrichia and photophobia; KP, keratosis pilaris; LGMN, legumain; LI, lamellar ichthyosis; qPCR, real-time quantitative PCR; shRNA, short hairpin RNA.
KW - Human skin equivalents
KW - Ichthyosis
KW - Lentivirus
KW - Protease inhibitor
KW - Short hairpin RNA
U2 - 10.1111/exd.12022
DO - 10.1111/exd.12022
M3 - Letter
C2 - 23163660
AN - SCOPUS:84871907837
SN - 0906-6705
VL - 21
SP - 889
EP - 891
JO - Experimental Dermatology
JF - Experimental Dermatology
IS - 11
ER -
