Transcriptional analyses of two mouse models of spina bifida
Article first published online: 28 SEP 2012
Copyright © 2012 Wiley Periodicals, Inc.
Birth Defects Research Part A: Clinical and Molecular Teratology
Special Issue: Papers from the 7th International Neural Tube Defects Conference
Volume 94, Issue 10, pages 782–789, October 2012
How to Cite
Cabrera, R. M., Finnell, R. H., Zhu, H., Shaw, G. M. and Wlodarczyk, B. J. (2012), Transcriptional analyses of two mouse models of spina bifida. Birth Defects Research Part A: Clinical and Molecular Teratology, 94: 782–789. doi: 10.1002/bdra.23081
- Issue published online: 16 OCT 2012
- Article first published online: 28 SEP 2012
- Manuscript Accepted: 8 AUG 2012
- Manuscript Revised: 3 AUG 2012
- Manuscript Received: 6 MAR 2012
- National Institutes of Health. Grant Numbers: DE016315, NS050249
- spina bifida;
- gene expression;
- mouse mutants
Spina bifida is one of the most common of all human structural birth defects. Despite considerable effort over several decades, the causes and mechanisms underlying this malformation remain poorly characterized.
To better understand the pathogenesis of this abnormality, we conducted a microarray study using Mouse Whole Genome Bioarrays which have ∼36,000 gene targets, to compare gene expression profiles between two mouse models; CXL-Splotch and FKBP8Gt(neo) which express a similar spina bifida phenotype. We anticipated that there would be a collection of overlapping genes or shared genetic pathways at the molecular level indicative of a common mechanism underlying the pathogenesis of spina bifida during embryonic development.
A total of 54 genes were determined to be differentially expressed (25 downregulated, 29 upregulated) in the FKBP8Gt(neo) mouse embryos; whereas 73 genes were differentially expressed (56 downregulated, 17 upregulated) in the CXL-Splotch mouse relative to their wild-type controls. Remarkably, the only two genes that showed decreased expression in both mutants were v-ski sarcoma viral oncogene homolog (Ski), and Zic1, a transcription factor member of the zinc finger family. Confirmation analysis using quantitative real-time (qRT)-PCR indicated that only Zic1 was significantly decreased in both mutants. Gene ontology analysis revealed striking enrichment of genes associated with mesoderm and central nervous system development in the CXL-Splotch mutant embryos, whereas in the FKBP8Gt(neo) mutants, the genes involved in dorsal/ventral pattern formation, cell fate specification, and positive regulation of cell differentiation were most likely to be enriched. These results indicate that there are multiple pathways and gene networks perturbed in mouse embryos with shared phenotypes. Birth Defects Research (Part A) 2012. © 2012 Wiley Periodicals, Inc.