{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:07:28Z","timestamp":1785434848778,"version":"3.56.0"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Autosomal recessive nonsyndromic epidermal differentiation disorders (AR\u2010nEDDs), also known as autosomal recessive congenital ichthyosis (ARCI), are rare genetic skin diseases that lack curative treatments and can only be managed symptomatically. Their study is hampered by the limited availability of biological samples and donor tissues. Artificial skin models offer a valuable alternative for experimental research. Here, we generated epidermal skin equivalents (ESE) using primary keratinocytes from patients with AR\u2010nEDDs carrying pathogenic variants in\n                    <jats:italic>ALOX12B<\/jats:italic>\n                    ,\n                    <jats:italic>CYP4F22<\/jats:italic>\n                    , and\n                    <jats:italic>CERS3<\/jats:italic>\n                    , as well as immortalized N\/TERT\u20102G cells. Whereas primary cells undergo senescence, N\/TERT\u20102G cells offer a promising alternative to overcome this limitation. Histological staining and qPCR were applied to assess key epidermal proteins and AR\u2010nEDD\u2010related gene expression in patient\u2010 and control\u2010derived models. Patient\u2010derived ESE reproduced the major histopathological features and protein expression patterns characteristic of AR\u2010nEDDs. In contrast, N\/TERT\u20102G\u2010based models showed earlier expression of 12R\u2010LOX, CYP4F22, and CERS3 proteins in epidermal layers compared to healthy donor equivalents. These findings suggest that N\/TERT\u20102G cells represent a reproducible platform for future gene\u2010editing approaches of modelling epidermal differentiation disorders. However, as they do not inherently carry pathogenic variants, they are particularly suitable for gene\u2010editing approaches such as CRISPR\/Cas9\u2010mediated disease modelling. Conversely, patient\u2010derived keratinocyte models remain indispensable for validating disease mechanisms and evaluating therapeutic strategies.\n                  <\/jats:p>","DOI":"10.1111\/exd.70298","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T13:20:27Z","timestamp":1781529627000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Potential of 3D Skin Models and N\/TERT\u20102G Cell Line in Genetic Research on Autosomal Recessive Nonsyndromic Epidermal Differentiation Disorders"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8924-7239","authenticated-orcid":false,"given":"Hao\u2010Hsiang","family":"Hsu\u2010Rehder","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, Medical Center\u2014University of Freiburg, Faculty of Medicine University of Freiburg  Freiburg Germany"},{"name":"Competence Center for Cornification Disorders, Freiburg Center for Rare Diseases University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5077-3034","authenticated-orcid":false,"given":"Cristina","family":"Glocker","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Medical Center\u2014University of Freiburg, Faculty of Medicine University of Freiburg  Freiburg Germany"},{"name":"Competence Center for Cornification Disorders, Freiburg Center for Rare Diseases University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7987-9983","authenticated-orcid":false,"given":"Christine","family":"Aldrian","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Medical Center\u2014University of Freiburg, Faculty of Medicine University of Freiburg  Freiburg Germany"},{"name":"Competence Center for Cornification Disorders, Freiburg Center for Rare Diseases University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5530-020X","authenticated-orcid":false,"given":"Ezgi","family":"Dikici","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Medical Center\u2014University of Freiburg, Faculty of Medicine University of Freiburg  Freiburg Germany"},{"name":"Competence Center for Cornification Disorders, Freiburg Center for Rare Diseases University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0619-7004","authenticated-orcid":false,"given":"Gesa Sophie","family":"Wilde","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Medical Center\u2014University of Freiburg, Faculty of Medicine University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9322-5257","authenticated-orcid":false,"given":"Mariana","family":"Stavila","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Medical Center\u2014University of Freiburg, Faculty of Medicine University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3602-0102","authenticated-orcid":false,"given":"Nathalie","family":"Jonca","sequence":"additional","affiliation":[{"name":"Toulouse Institute for Infectious and Inflammatory Diseases Toulouse University, CNRS, Inserm  Toulouse France"},{"name":"Department of Cell Biology and Cytology, Federative Institute of Biology, Purpan Hospital University Hospital  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6668-7798","authenticated-orcid":false,"given":"Branislav","family":"Koll\u00e1r","sequence":"additional","affiliation":[{"name":"Department of Plastic and Hand Surgery, Faculty of Medicine Medical Center \u2013 University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4471-3160","authenticated-orcid":false,"given":"Steffen Ulrich","family":"Eisenhardt","sequence":"additional","affiliation":[{"name":"Department of Plastic and Hand Surgery, Faculty of Medicine Medical Center \u2013 University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8580-8118","authenticated-orcid":false,"given":"Judith","family":"Fischer","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Medical Center\u2014University of Freiburg, 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