Transcriptional analyses of two mouse models of spina bifida

Birth Defects Res A Clin Mol Teratol. 2012 Oct;94(10):782-9. doi: 10.1002/bdra.23081. Epub 2012 Sep 28.


Background: 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.

Methods: 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 FKBP8(Gt(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.

Results: 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 FKBP8(Gt(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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Embryo, Mammalian
  • Female
  • Gene Expression Profiling*
  • Humans
  • Mice*
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microarray Analysis
  • PAX3 Transcription Factor
  • Paired Box Transcription Factors / genetics
  • Pregnancy
  • Spinal Dysraphism / genetics*
  • Spinal Dysraphism / pathology
  • Tacrolimus Binding Proteins / genetics
  • Transcription, Genetic


  • Fkbp8 protein, mouse
  • PAX3 Transcription Factor
  • Paired Box Transcription Factors
  • Pax3 protein, mouse
  • Tacrolimus Binding Proteins