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Title: Hif1α down-regulation is associated with transposition of great arteries in mice treated with a RA antagonist      
availability:
available
aggregation:
instance of dataset
privacy:
not applicable
refinement:
curated
dateReleased:
05-02-2014
ID:
E-GEOD-19012
description:
Aims: Congenital heart defect (CHD) account for 25% of all human congenital abnormalities. Very few CHD-causing genes have been identified so far; so, to discover further genes we performed a global transcriptome analysis in mouse models of CHD. Methods and results: By the use of a retinoic acid competitive antagonist (BMS-189453) we caused CHD, thymic abnormalities and neural tube defects in mouse newborns. Transposition of great arteries was the prevalent cardiac defect observed (61%). Recently we were able to partially rescue this abnormal phenotype by oral administration of folic acid. Now we have performed a microarray analysis in mouse embryos (8.5 dpc) treated with BMS-189453 alone and with BMS-189453 plus folic acid (FA). On the basis of microarray and QRT-PCR results, we deeper analysed Hif1α because of its down-regulation in BMS-treated embryos vs WT and its increased expression level in BMS+FA treated embryos compared to BMS-treated ones. Immunofluorescence experiments confirmed the under-expression of Hif1α protein in BMS-treated embryos compared to WT and BMS+FA treated ones and moreover demonstrated that at 8.5 dpc Hif1α is mainly expressed in the embryo’s heart. Conclusion: We propose that Hif1α down-regulation by blocking retinoic acid binding, may contribute to the development of the cardiac defects of mouse newborns. In line with our hypothesis, when Hif1α expression level is restored (by supplementation of folic acid) a decrement of CHD is found. At the best of our knowledge this is the first report that link retinoic acid metabolism to Hif1α regulation and the development of TGA 2 samples w/ 2 dye-swaps
keywords:
transcription profiling by array
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storedIn:
Array Express
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accessType:
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primary:
true
accessURL: https://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-19012
format:
JSON
storedIn:
OmicsDI
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not compressed
accessType:
download
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none
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primary:
false
accessURL: www.omicsdi.org/ws/dataset/arrayexpress-repository/E-GEOD-19012.json
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XML
storedIn:
OmicsDI
qualifier:
not compressed
accessType:
download
authorization:
none
authentication:
none
primary:
false
accessURL: http://www.omicsdi.org/ws/dataset/arrayexpress-repository/E-GEOD-19012.xml
ID:
SCR:014747
name:
Omics Discovery Index
abbreviation:
OmicsDI
homePage: http://www.omicsdi.org/