Cecr2 mutations causing exencephaly trigger misregulation of mesenchymal/ectodermal transcription factors
| Autor: | Heather E. McDermid, Kirst King-Jones, Farshad H. Niri, Christine E. Dawe, Nicholas A. Fairbridge, Megan K. Kooistra |
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| Rok vydání: | 2010 |
| Předmět: |
Embryology
Transcription Genetic Mutant Down-Regulation Exencephaly Biology medicine.disease_cause Facial Bones Mesoderm Mice Prosencephalon Pregnancy Ectoderm medicine Animals Neural Tube Defects Transcription factor Encephalocele Mice Inbred BALB C Mutation Microarray analysis techniques Neural tube Gene Expression Regulation Developmental General Medicine medicine.disease Molecular biology Penetrance Null allele Up-Regulation medicine.anatomical_structure Pediatrics Perinatology and Child Health Intercellular Signaling Peptides and Proteins Female Transcription Factors Developmental Biology |
| Zdroj: | Birth Defects Research Part A: Clinical and Molecular Teratology. 88:619-625 |
| ISSN: | 1542-0752 |
| DOI: | 10.1002/bdra.20695 |
| Popis: | BACKGROUND: Over 200 mouse genes are associated with neural tube defects (NTDs), including Cecr2, the bromodomain-containing subunit of the CERF chromatin remodeling complex. METHODS: Gene-trap mutation Cecr2Gt45Bic results in 74% exencephaly (equivalent of human anencephaly) on the BALB/c strain. Gene expression altered during cranial neural tube closure by the Cecr2 mutation was identified through microarray analysis of 11–14 somites stage Cecr2Gt45Bicembryos. RESULTS: Analysis of Affymetrix Mouse 430 2.0 chips detected 60 transcripts up-regulated and 54 transcripts down-regulated in the Cecr2Gt45Bic embryos (fold > 1.5, p < 0.05). The Cecr2 transcript was reduced only ∼7- to 14-fold from normal levels, suggesting the Cecr2Gt45Bic is a hypomorphic mutation. We therefore generated a novel Cecr2 null allele (Cecr2tm1.1Hemc). Resulting mutants displayed a stronger penetrance of exencephaly than Cecr2Gt45Bic in both BALB/c and FVB/N strains, in addition to midline facial clefts and forebrain encephalocele in the FVB/N strain. The Cecr2 transcript is reduced 260-fold in the Cecr2tm1.1Hemc line. Subsequent qRT-PCR using Cecr2tm1.1Hemc mutant heads confirmed downregulation of transcription factors Alx1/Cart1,Dlx5, Eya1, and Six1. CONCLUSIONS: As both Alx1/Cart1 and Dlx5 mouse mutations result in exencephaly, we hypothesize that changes in expression of these mesenchymal/ectodermal transcription factors may contribute to NTDs associated with Cecr2. Birth Defects Research (Part A), 2010. © 2010 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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