Journal
PHYSIOLOGICAL GENOMICS
Volume 44, Issue 1, Pages 35-46Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/physiolgenomics.00124.2011
Keywords
neural tube defect; mouse; Arhgap19; microarray; subinterval congenics
Categories
Funding
- Canadian Institutes of Health Research (CIHR) [MOP64361]
- WCHRI (Women and Children's Health Research Institute) [RES00002890]
- Natural Sciences and Engineering Research Council of Canada (NSERC)
- Alberta Heritage Foundation for Medical Research
Ask authors/readers for more resources
Kooistra MK, Leduc RYM, Dawe CE, Fairbridge NA, Rasmussen J, Man JHY, Bujold M, Juriloff D, King-Jones K, McDermid HE. Strain-specific modifier genes of Cecr2-associated exencephaly in mice: genetic analysis and identification of differentially expressed candidate genes. Physiol Genomics 44: 35-46, 2012. First published November 1, 2011; doi:10.1152/physiolgenomics.00124.2011.-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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available