Dataset Information


Expression and Metabolic Profiles in a Panel of Five Neural Tube Defect Mouse Models

ABSTRACT: Neural tube defects (NTDs) are serious birth defects with an estimated worldwide incidence of 1 per 1,000 live births. The multifactorial nature of NTDs in humans has made it difficult to elucidate pathogenesis mechanisms. However, a strong relationship has been established between folate-homocysteine metabolism and NTD risk. Prevention of a substantial proportion of fetal NTDs can be achieved through maternal folic acid (FA) supplementation. However the mechanism by which FA exerts its beneficial effect remains unclear. METHODS: To improve our understanding of the underlying mechanisms of NTD pathogenesis and the ways in which folate exerts its beneficial effect, we analyzed mRNA profiles as well as folate and vitamin B12 levels in five NTD mouse mutants whose response to dietary FA was previously established. RESULTS: Differentially expressed genes representing the effect of each NTD-causing mutation were identified and associated with biologic pathways. Interestingly, the panel of NTD mutants collectively revealed pathways related to two nuclear receptors, retinoid X receptor (RXR) and pregnane X receptor (PXR), suggesting that these pathways may be related to a shared mechanism of NTD development. Moreover, the NTD-causing mutations that were associated with FA responsiveness had expression profiles that were related to folate-homocysteine metabolic pathways. These pathways were not strongly associated with mutants that do not respond to FA supplementation, implying that FA may be beneficial when the NTD mutation affects pathways related to folate-homocysteine metabolism. 5 groups of NTD mutants were studied. From each mutant group Heterozygous (test) and wild-type (control) female pups were used for this study at 6-8 weeks of age. 4 biological replicates were used for each of the test and control groups of each mutant. All mice used for the experiments were fasted 4-5 hours before dissection. A total of 36 samples were analyzed.

ORGANISM(S): Mus musculus  

SUBMITTER: Donald W Jacobsen   Joseph H Nadeau  Ghunwa A Nakouzi  Joseph Nadeau  Patricia M DiBello 

PROVIDER: E-GEOD-51285 | ArrayExpress | 2013-09-30



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