{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T02:08:22Z","timestamp":1779934102270,"version":"3.53.1"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T00:00:00Z","timestamp":1772841600000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR072621"],"award-info":[{"award-number":["R01AR072621"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["F31AR083693"],"award-info":[{"award-number":["F31AR083693"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Ankyloblepharon\u2010ectodermal defects\u2010cleft lip\/palate (AEC) is a disorder caused by autosomal\u2010dominant mutations in the\n                    <jats:italic>TP63<\/jats:italic>\n                    gene. AEC is characterised by the presence of severe and painful skin erosions that can take years to heal. Current treatment options for these devastating lesions are limited, highlighting the need for new therapeutic strategies. We previously generated keratinocytes from patient\u2010derived induced pluripotent stem cells (iPSC\u2010K) and identified defects in several cell adhesion complexes, including desmosomes, hemidesmosomes and focal adhesions. In the present study, we developed a complementary in\u00a0vitro model using NTERT keratinocytes transduced with lentiviral constructs expressing AEC\u2010related\n                    <jats:italic>TP63<\/jats:italic>\n                    mutations (N\u2010AEC). This model allows for the large\u2010scale production of disease\u2010relevant material, overcoming the limitations of iPSC\u2010derived keratinocytes, which have the characteristics of primary keratinocytes, including limited cell doublings and lifespan. We demonstrate that N\u2010AEC keratinocytes exhibit key defects observed in AEC iPSC\u2010K and AEC patient skin, including downregulation of cell adhesion proteins. In addition, 3D epidermal equivalents generated from these cells replicate pathological features seen in AEC patient skin, such as intra\u2010epidermal cysts, reduced desmosomal protein expression and altered expression of differentiation markers. Our N\u2010AEC model provides a valuable tool for investigating the mechanisms underlying skin fragility in AEC and other genetic skin disorders and advances the potential for novel therapeutic development.\n                  <\/jats:p>","DOI":"10.1111\/exd.70238","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T19:32:13Z","timestamp":1772998333000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel Model System to Identify Cellular and Molecular Defects Underlying Rare Genetic Disorders"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7421-9513","authenticated-orcid":false,"given":"Maddison N.","family":"Salois","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Brody School of Medicine East Carolina University  Greenville North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saiphone","family":"Webb","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Brody School of Medicine East Carolina University  Greenville North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaiah A.","family":"Proctor","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Brody School of Medicine East Carolina University  Greenville North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Koch","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Brody School of Medicine East Carolina University  Greenville North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maranke I.","family":"Koster","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Brody School of Medicine East Carolina University  Greenville North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,7]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.3.221"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2010.119"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/19539"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/19531"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32797"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32794"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102133.2012.10888.x"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.141.12.1567"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.14885"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201100199"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36455"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2018.02.016"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpz1.408"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1346\u20108138.2004.tb00654.x"},{"key":"e_1_2_11_16_1","first-page":"95","volume-title":"Progress in Molecular Biology and Translational Science","author":"Kowalczyk A. 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