Haploinsufficiency of interferon regulatory factor 6 alters brain morphology in the mouse. Issue 3 (19th December 2013)

• Record Type: Journal Article
• Authors: Aerts, Andrea; DeVolder, Ian; Weinberg, Seth M.; Thedens, Dan; Dunnwald, Martine; Schutte, Brian C.; Nopoulos, Peg
• Is Part Of: American journal of medical genetics. Volume 164:Issue 3(2014.)
• Page Start: 655
• Page End: 660
• Publication Date: 2013-12-19
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.36333
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ajmga36333-sec-0001" sec-type="section"> <p>Orofacial clefts are among the commonest birth defects. Among many genetic contributors to orofacial clefting, Interferon Regulatory Factor 6 (<italic>IRF6</italic>) is unique since mutations in this gene cause Van der Woude (VWS), the most common clefting syndrome. Furthermore, variants in <italic>IRF6</italic> contribute to increased risk for non‐syndromic 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 <italic>Irf6</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 (<italic>Irf6</italic><sup><italic>gt1/+</italic></sup>; n = 9) and wild‐type (<italic>Irf6</italic><sup><italic>+/+</italic></sup>; n = 6) mice at comparable age underwent a 4.7‐T 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 <italic>Irf6</italic><sup><italic>gt1/+</italic></sup> mice compared to that of wild types (<italic>P</italic> = 0.028) while the posterior cortex did not differ. In addition, the volume of the cerebellum of <italic>Irf6</italic><sup><italic>gt1/+</italic></sup> mice was decreased (<italic>P</italic> = 0.004). Mice that were heterozygous for <italic>Irf6</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 <italic>IRF6</italic> in brain morphometry and provide evidence for a potential genetic link to abnormal brain development in orofacial clefting. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>