Strain-specific modifier genes of Cecr2-associated exencephaly in mice: genetic analysis and identification of differentially expressed candidate genes
| Autor: | Christine E. Dawe, Diana M. Juriloff, Megan K. Kooistra, Renee Y.M. Leduc, Mattea Bujold, Nicholas A. Fairbridge, Jay Rasmussen, Kirst King-Jones, Julie H.Y. Man, Heather E. McDermid |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Candidate gene Microarray Physiology Exencephaly Biology Genetic analysis Mice Species Specificity Genetics medicine Animals Humans Neural Tube Defects Gene Genetic Association Studies Mice Inbred BALB C Genes Modifier Neural tube defect Strain (biology) Gene Expression Profiling Neural tube Chromosome Mapping Gene Expression Regulation Developmental medicine.disease Embryo Mammalian Mice Mutant Strains Mice Inbred C57BL medicine.anatomical_structure Intercellular Signaling Peptides and Proteins Female Transcription Factors |
| Zdroj: | Physiological genomics. 44(1) |
| ISSN: | 1531-2267 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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