{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T19:47:21Z","timestamp":1790970441491,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,7,19]],"date-time":"2017-07-19T00:00:00Z","timestamp":1500422400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["F31DE022696\u201001"],"award-info":[{"award-number":["F31DE022696\u201001"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["DE13513"],"award-info":[{"award-number":["DE13513"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007709","name":"MSU","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007709","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Developmental Dynamics"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:p><jats:bold><jats:styled-content>Background:<\/jats:styled-content><\/jats:bold> Mutations in <jats:italic>IRF6<\/jats:italic>, <jats:italic>CHUK (IKKA),<\/jats:italic> and <jats:italic>RIPK4<\/jats:italic> can lead to a disease spectrum that includes cutaneous, limb, and craniofacial malformations. Loss of these alleles in the mouse leads to perinatal lethality and severe cutaneous, limb, and craniofacial defects also. Genetic rescue in the mouse has been shown for <jats:italic>Ikka<\/jats:italic> and <jats:italic>Ripk4<\/jats:italic>. <jats:bold><jats:styled-content>Results:<\/jats:styled-content><\/jats:bold> Here, we show partial genetic rescue of <jats:italic>Irf6<\/jats:italic> knockout embryos using the <jats:italic>KRT14<\/jats:italic> promoter to drive <jats:italic>Irf6<\/jats:italic> expression in the basal epithelium. In contrast to <jats:italic>Irf6<\/jats:italic> knockout embryos, rescue embryos survive the immediate perinatal period. Macroscopic examination reveals rescue of skin adhesions between the axial and appendicular skeleton. Unexpectedly, <jats:italic>KRT14\u2010driven Irf6<\/jats:italic> expression does not completely rescue orofacial clefting and adhesions between the palate and tongue, suggesting the importance of cell\u2010autonomous IRF6 expression in periderm. Like knockout embryos, <jats:italic>Irf6<\/jats:italic> rescue embryos also have persistent esophageal adhesions, which likely contribute to postnatal demise. <jats:bold><jats:styled-content>Conclusions:<\/jats:styled-content><\/jats:bold> Together, these data suggest that targeted expression of IRF6 can significantly reduce disease severity, but that a minimum level of <jats:italic>Irf6<\/jats:italic> in both periderm and basal epithelial cells is necessary for orofacial development. Therefore, homologous human and mouse phenotypes are observed for IRF6, IKKA, and RIPK4. In this work, we show that altering the expression level of IRF6 dramatically modified this phenotype in utero. <jats:italic>Developmental Dynamics 246:670\u2013681, 2017<\/jats:italic>. \u00a9 2017 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/dvdy.24537","type":"journal-article","created":{"date-parts":[[2017,6,23]],"date-time":"2017-06-23T04:10:34Z","timestamp":1498191034000},"page":"670-681","source":"Crossref","is-referenced-by-count":18,"title":["IRF6 expression in basal epithelium partially rescues <i>Irf6<\/i> knockout mice"],"prefix":"10.1002","volume":"246","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6049-8144","authenticated-orcid":false,"given":"Youssef A.","family":"Kousa","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Michigan State University East Lansing Michigan"},{"name":"Pediatric Residency Program Children's National Health System Washington DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina","family":"Moussa","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics Michigan State University East Lansing Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian C.","family":"Schutte","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Michigan State University East Lansing Michigan"},{"name":"Department of Microbiology and Molecular Genetics Michigan State University East Lansing Michigan"},{"name":"Department of Pediatrics and Human Development Michigan State University East Lansing Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,7,19]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1110931108"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.067082"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2012.269"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt664"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.22786"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0056270"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(02)01075-8"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5412.316"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1903"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.089615"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng985"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.24341"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.156.2.644"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2013.09.022"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36896"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2011.56"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.11.009"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.242"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1894"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp201"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI71946"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2009.223"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02421"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.107.2.427"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1208130"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5412.313"},{"key":"e_1_2_6_28_1","first-page":"176","article-title":"Closure of the secondary palate in three strains of mice","volume":"4","author":"Walker BE","year":"1956","journal-title":"J Embryol Exp Morphol"},{"key":"e_1_2_6_29_1","first-page":"313","article-title":"Targeted expression of activated erbB\u20102 to the epidermis of transgenic mice elicits striking developmental abnormalities in the epidermis and hair follicles","volume":"9","author":"Xie W","year":"1998","journal-title":"Cell Growth Differ"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032909"}],"container-title":["Developmental Dynamics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fdvdy.24537","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/anatomypubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dvdy.24537","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T01:05:44Z","timestamp":1760403944000},"score":1,"resource":{"primary":{"URL":"https:\/\/anatomypubs.onlinelibrary.wiley.com\/doi\/10.1002\/dvdy.24537"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7,19]]},"references-count":29,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2017,9]]}},"alternative-id":["10.1002\/dvdy.24537"],"URL":"https:\/\/doi.org\/10.1002\/dvdy.24537","archive":["Portico"],"relation":{},"ISSN":["1058-8388","1097-0177"],"issn-type":[{"value":"1058-8388","type":"print"},{"value":"1097-0177","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7,19]]}}}