Periodical
Cecr2mutations causing exencephaly trigger misregulation of mesenchymalectodermal transcription factors
| العنوان: | Cecr2mutations causing exencephaly trigger misregulation of mesenchymalectodermal transcription factors |
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| المؤلفون: | Fairbridge, Nicholas A., Dawe, Christine E., Niri, Farshad H., Kooistra, Megan K., KingJones, Kirst, McDermid, Heather E. |
| المصدر: | Birth Defects Research Part A: Clinical and Molecular Teratology; August 2010, Vol. 88 Issue: 8 p619-625, 7p |
| مستخلص: | BACKGROUND:Over 200 mouse genes are associated with neural tube defects NTDs, including Cecr2,the bromodomaincontaining subunit of the CERF chromatin remodeling complex. METHODS:Genetrap mutation Cecr2Gt45Bicresults in 74 exencephaly equivalent of human anencephaly on the BALBc strain. Gene expression altered during cranial neural tube closure by the Cecr2mutation was identified through microarray analysis of 11–14 somites stage Cecr2Gt45Bicembryos. RESULTS:Analysis of Affymetrix Mouse 430 2.0 chips detected 60 transcripts upregulated and 54 transcripts downregulated in the Cecr2Gt45Bicembryos fold > 1.5, p< 0.05. The Cecr2transcript was reduced only ∼7 to 14fold from normal levels, suggesting the Cecr2Gt45Bicis a hypomorphic mutation. We therefore generated a novel Cecr2null allele Cecr2tm1.1Hemc. Resulting mutants displayed a stronger penetrance of exencephaly than Cecr2Gt45Bicin both BALBc and FVBN strains, in addition to midline facial clefts and forebrain encephalocele in the FVBN strain. The Cecr2transcript is reduced 260fold in the Cecr2tm1.1Hemcline. Subsequent qRTPCR using Cecr2tm1.1Hemcmutant heads confirmed downregulation of transcription factors Alx1Cart1,Dlx5, Eya1,and Six1. CONCLUSIONS:As both Alx1Cart1and Dlx5mouse mutations result in exencephaly, we hypothesize that changes in expression of these mesenchymalectodermal transcription factors may contribute to NTDs associated with Cecr2. Birth Defects Research Part A, 2010. © 2010 WileyLiss, Inc. |
| قاعدة البيانات: | Supplemental Index |
| تدمد: | 15420752 15420760 |
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| DOI: | 10.1002/bdra.20695 |