title: Cecr2 mutations causing exencephaly trigger misregulation of mesenchymal/ectodermal transcription factors.
abstract: 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 Cecr2(Gt45Bic) 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 Cecr2(Gt45Bic)embryos.
  
  
  RESULTS
  Analysis of Affymetrix Mouse 430 2.0 chips detected 60 transcripts up-regulated and 54 transcripts down-regulated in the Cecr2(Gt45Bic) embryos (fold > 1.5, p < 0.05). The Cecr2 transcript was reduced only approximately 7- to 14-fold from normal levels, suggesting the Cecr2(Gt45Bic) is a hypomorphic mutation. We therefore generated a novel Cecr2 null allele (Cecr2 (tm1.1Hemc)). Resulting mutants displayed a stronger penetrance of exencephaly than Cecr2(Gt45Bic) 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 Cecr2(tm1.1Hemc) line. Subsequent qRT-PCR using Cecr2 (tm1.1Hemc) 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.
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Canada.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Fairbridge
authors.forename: Christine E
authors.initials: CE
authors.lastname: Dawe
authors.forename: Farshad H
authors.initials: FH
authors.lastname: Niri
authors.forename: Megan K
authors.initials: MK
authors.lastname: Kooistra
authors.forename: Kirst
authors.initials: K
authors.lastname: King-Jones
authors.forename: Heather E
authors.initials: HE
authors.lastname: McDermid
mesh_terms: D000818:Animals; D015536:Down-Regulation / Q000235:genetics; D004475:Ectoderm / Q000378:metabolism* / Q000503:physiopathology; D004677:Encephalocele / Q000378:metabolism; D005147:Facial Bones / Q000002:abnormalities; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008648:Mesoderm / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D009436:Neural Tube Defects / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D011247:Pregnancy; D016548:Prosencephalon / Q000002:abnormalities; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000235:genetics
chemical_list: C501837:CECR2 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D014157:Transcription Factors