title: Strain-specific modifier genes of Cecr2-associated exencephaly in mice: genetic analysis and identification of differentially expressed candidate genes.
abstract: Although neural tube defects (NTDs) are common in humans, little is known about their multifactorial genetic causes. While most mouse models involve NTDs caused by a single mutated gene, we have previously described a multigenic system involving susceptibility to NTDs. In mice with a mutation in Cecr2, the cranial NTD exencephaly shows strain-specific differences in penetrance, with 74% penetrance in BALB/cCrl and 0% penetrance in FVB/N. Whole genome linkage analysis showed that a region of chromosome 19 was partially responsible for this difference in penetrance. We now reveal by genetic analysis of three subinterval congenic lines that the chromosome 19 region contains more than one modifier gene. Analysis of embryos showed that although a Cecr2 mutation causes wider neural tubes in both strains, FVB/N embryos overcome this abnormality and close. A microarray analysis comparing neurulating female embryos from both strains identified differentially expressed genes within the chromosome 19 region, including Arhgap19, which is expressed at a lower level in BALB/cCrl due to a stop codon specific to that substrain. Modifier genes in this region are of particular interest because a large portion of this region is syntenic to human chromosome 10q25, the site of a human susceptibility locus.
authors: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors: Megan K
authors: MK
authors: Kooistra
authors: Renee Y M
authors: RY
authors: Leduc
authors: Christine E
authors: CE
authors: Dawe
authors: Nicholas A
authors: NA
authors: Fairbridge
authors: Jay
authors: J
authors: Rasmussen
authors: Julie H Y
authors: JH
authors: Man
authors: Mattea
authors: M
authors: Bujold
authors: Diana
authors: D
authors: Juriloff
authors: Kirst
authors: K
authors: King-Jones
authors: Heather E
authors: HE
authors: McDermid
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D004622:Embryo, Mammalian; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D060045:Genes, Modifier / Q000502:physiology*; D056726:Genetic Association Studies; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009436:Neural Tube Defects / Q000235:genetics* / Q000473:pathology; D013045:Species Specificity; D014157:Transcription Factors
chemical_list: C501837:CECR2 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D014157:Transcription Factors