Journal article
Haploinsufficiency of interferon regulatory factor 6 alters brain morphology in the mouse
American journal of medical genetics. Part A, Vol.164A(3), pp.655-660
03/2014
DOI: 10.1002/ajmg.a.36333
PMCID: PMC4100789
PMID: 24357509
Abstract
Orofacial clefts are among the commonest birth defects. Among many genetic contributors to orofacial clefting, Interferon Regulatory Factor 6 (IRF6) is unique since mutations in this gene cause Van der Woude (VWS), the most common clefting syndrome. Furthermore, variants in IRF6 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 Irf6 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 (Irf6(gt1/+); n = 9) and wild-type (Irf6(+/+) ; 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 Irf6(gt1/+) mice compared to that of wild types (P = 0.028) while the posterior cortex did not differ. In addition, the volume of the cerebellum of Irf6(gt1/+) mice was decreased (P = 0.004). Mice that were heterozygous for Irf6 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 IRF6 in brain morphometry and provide evidence for a potential genetic link to abnormal brain development in orofacial clefting.
Details
- Title: Subtitle
- Haploinsufficiency of interferon regulatory factor 6 alters brain morphology in the mouse
- Creators
- Andrea Aerts - Department of Psychiatry, University of Iowa, Iowa City, IowaIan DeVolderSeth M WeinbergDan ThedensMartine DunnwaldBrian C SchuttePeg Nopoulos
- Resource Type
- Journal article
- Publication Details
- American journal of medical genetics. Part A, Vol.164A(3), pp.655-660
- DOI
- 10.1002/ajmg.a.36333
- PMID
- 24357509
- PMCID
- PMC4100789
- NLM abbreviation
- Am J Med Genet A
- ISSN
- 1552-4825
- eISSN
- 1552-4833
- Publisher
- United States
- Grant note
- AR-055313 / NIAMS NIH HHS R03 AR055313 / NIAMS NIH HHS
- Language
- English
- Date published
- 03/2014
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Neurology; Radiology; Electrical and Computer Engineering; Psychiatry; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center
- Record Identifier
- 9984025353302771
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