{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T09:54:39Z","timestamp":1791453279136,"version":"4.3.3"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T00:00:00Z","timestamp":1714953600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The transmembrane protein claudin\u20101 is critical for formation of the epidermal barrier structure called tight junctions (TJ) and has been shown to be important in multiple disease states. These include neonatal ichthyosis and sclerosing cholangitis syndrome, atopic dermatitis\u00a0and various viral infections. To develop a model to investigate the role of claudin\u20101 in different disease settings, we used CRISPR\/Cas9 to generate human immortalized keratinocyte (KC) lines lacking claudin\u20101 (CLDN1 KO). We then determined whether loss of claudin\u20101 expression affects epidermal barrier formation\/function and KC differentiation\/stratification. The absence of claudin\u20101 resulted in significantly reduced barrier function in both monolayer and organotypic cultures. CLDN1 KO cells demonstrated decreases in gene transcripts encoding the barrier protein filaggrin and the differentiation marker cytokeratin\u201010. Marked morphological differences were also observed in CLDN1 KO organotypic cultures including diminished stratification and reduced formation of the <jats:italic>stratum granulosum<\/jats:italic>. We also detected increased proliferative KC in the basale layer of CLDN1 KO organotypic cultures. These results further support the role of claudin\u20101 in epidermal barrier and suggest an additional role of this protein in appropriate stratification of the epidermis.<\/jats:p>","DOI":"10.1111\/exd.15084","type":"journal-article","created":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T04:34:33Z","timestamp":1715056473000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["<i>CLDN1<\/i> knock out keratinocytes as a model to investigate multiple skin disorders"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7633-8732","authenticated-orcid":false,"given":"Kimberly A.","family":"Arnold","sequence":"first","affiliation":[{"name":"Department of Dermatology University of Rochester Medical Center  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6456-082X","authenticated-orcid":false,"given":"Mary C.","family":"Moran","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Rochester Medical Center  Rochester New York USA"},{"name":"Department of Microbiology and Immunology University of Rochester Medical Center  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2231-7151","authenticated-orcid":false,"given":"Huishan","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Rochester Medical Center  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3522-2573","authenticated-orcid":false,"given":"Ivonne M. J. J.","family":"van Vlijmen\u2010Willems","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Radboud University Medical Center Radboud Institute for Molecular Life Sciences (RIMLS)  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7752-6209","authenticated-orcid":false,"given":"Diana","family":"Rodijk\u2010Olthuis","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Radboud University Medical Center Radboud Institute for Molecular Life Sciences (RIMLS)  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0915-8624","authenticated-orcid":false,"given":"Jos P. H.","family":"Smits","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Radboud University Medical Center Radboud Institute for Molecular Life Sciences (RIMLS)  Nijmegen The Netherlands"},{"name":"Department of Dermatology, University Hospital D\u00fcsseldorf, Medical Faculty Heinrich Heine University  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7631-5234","authenticated-orcid":false,"given":"Matthew G.","family":"Brewer","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Rochester Medical Center  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.430130203"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700865"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12876053"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.142067"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200110122"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-58718-9"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1525474113"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.07.022"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.10.018"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.4.1436-1447.2000"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xjidi.2021.100018"},{"key":"e_1_2_11_13_1","first-page":"7","article-title":"Immortalized N\/TERT keratinocytes as an alternative cell source in 3D human epidermal models","volume":"7","author":"Smits JPH","year":"2017","journal-title":"Sci Rep\u2010Uk"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.171322.113"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2021.01.008"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20171626"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.12.052"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2010.390"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2017.09.055"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2014.83"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0144316"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2012.437"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41999-9"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910310104"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2012.507"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2013.01.002"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/21688370.2017.1336194"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2010.07.010"},{"key":"e_1_2_11_29_1","first-page":"67","article-title":"Epidermal changes in atopic dermatitis","volume":"114","author":"Neste D","year":"1985","journal-title":"Acta Derm Venereol Suppl (Stockh)"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2015.06.021"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.04.024"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-009-0457-0"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032713-120225"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0923-1811(02)00047-6"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1314768"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.08.009"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.19574"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.08.022"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2017.05.004"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2019.06.142"},{"issue":"2","key":"e_1_2_11_41_1","first-page":"917","article-title":"Coal tar induces AHR\u2010dependent skin barrier repair in atopic dermatitis","volume":"123","author":"Bogaard EH","year":"2013","journal-title":"J Clin Invest"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20174070"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xjidi.2022.100151"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpim.112"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"}],"container-title":["Experimental Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/exd.15084","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T12:40:10Z","timestamp":1720701610000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/exd.15084"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5]]},"references-count":44,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1111\/exd.15084"],"URL":"https:\/\/doi.org\/10.1111\/exd.15084","archive":["Portico"],"relation":{},"ISSN":["0906-6705","1600-0625"],"issn-type":[{"value":"0906-6705","type":"print"},{"value":"1600-0625","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5]]},"assertion":[{"value":"2023-02-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e15084"}}