{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T19:55:41Z","timestamp":1760385341105},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,12,19]],"date-time":"2013-12-19T00:00:00Z","timestamp":1387411200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:sec><jats:label \/><jats:p>Orofacial clefts are among the commonest birth defects. Among many genetic contributors to orofacial clefting, Interferon Regulatory Factor 6 (<jats:italic>IRF6<\/jats:italic>) is unique since mutations in this gene cause Van der Woude (VWS), the most common clefting syndrome. Furthermore, variants in <jats:italic>IRF6<\/jats:italic> contribute to increased risk for non\u2010syndromic cleft lip and\/or palate (NSCL\/P). Our previous work shows that individuals with either VWS or NSCL\/P may have cerebral anomalies (larger anterior, smaller posterior regions), and a smaller cerebellum. The objective of this study was to test the hypothesis that disrupting <jats:italic>Irf6<\/jats:italic> in the mouse will result in quantitative brain changes similar to those reported for humans with VWS and NSCL\/P. Male mice heterozygous for Irf6 (<jats:italic>Irf6<\/jats:italic><jats:sup><jats:italic>gt1\/+<\/jats:italic><\/jats:sup>; n\u2009=\u20099) and wild\u2010type (<jats:italic>Irf6<\/jats:italic><jats:sup><jats:italic>+\/+<\/jats:italic><\/jats:sup>; n\u2009=\u20096) mice at comparable age underwent a 4.7\u2010T MRI scan to obtain quantitative measures of cortical and subcortical brain structures. There was no difference in total brain volume between groups. However, the frontal cortex was enlarged in the <jats:italic>Irf6<\/jats:italic><jats:sup><jats:italic>gt1\/+<\/jats:italic><\/jats:sup> mice compared to that of wild types (<jats:italic>P<\/jats:italic>\u2009=\u20090.028) while the posterior cortex did not differ. In addition, the volume of the cerebellum of <jats:italic>Irf6<\/jats:italic><jats:sup><jats:italic>gt1\/+<\/jats:italic><\/jats:sup> mice was decreased (<jats:italic>P<\/jats:italic>\u2009=\u20090.004). Mice that were heterozygous for <jats:italic>Irf6<\/jats:italic> showed a similar pattern of brain anomalies previously reported in humans with VWS and NSCL\/P. These structural differences were present in the absence of overt oral clefts. These results support a role for <jats:italic>IRF6<\/jats:italic> in brain morphometry and provide evidence for a potential genetic link to abnormal brain development in orofacial clefting. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36333","type":"journal-article","created":{"date-parts":[[2013,12,19]],"date-time":"2013-12-19T20:16:25Z","timestamp":1387484185000},"page":"655-660","source":"Crossref","is-referenced-by-count":8,"title":["Haploinsufficiency of interferon regulatory factor 6 alters brain morphology in the mouse"],"prefix":"10.1002","volume":"164","author":[{"given":"Andrea","family":"Aerts","sequence":"first","affiliation":[{"name":"Department of Psychiatry University of Iowa Iowa City Iowa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian","family":"DeVolder","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Iowa Iowa City 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