Beta cell specific ablation of Foxa2 (HNF-3b) in mice - Study GBCO550
Genomics Study Specifications
|Study Name||Beta cell specific ablation of Foxa2 (HNF-3b) in mice|
|Contact Name||Klaus Kaestner (University of Pennsylvania)|
|My Strategies||Return to My Strategies page|
|Classification||Targets and roles of transcriptional regulators|
|BCBC Release Date||September 29, 2003|
|Public Release Date||September 29, 2003|
|Citation||Lantz KA, Vatamaniuk MZ, Brestelli JE, Friedman JR, Matschinsky FM, Kaestner KH. Foxa2 regulates multiple pathways of insulin secretion. J Clin Invest. 2004. 114:512-20|
Study to further characterize the genetic and functional consequence of the beta cell-specific ablation of Foxa2 (hepatocyte nuclear factor 3 beta, HNF-3b) in mice to better define the role of this gene in glucose homeostasis. The study involved 8 two-channel assays on PancChip 4.0, each consisting of a competitive mutant vs control hybridization. 4 control and 4 Foxa2loxP/loxP;Ins.CRE RNA samples were hybridized to the array using a dye-swap design. (The results from one of these assays had to be discarded from the analyses, so 7 assays were used.)
Study role of Foxa2 in regulation of insulin secretion by beta cells.
Conditional deletion of Foxa2 (Hnf 3beta) in a mouse model causes excessive insulin release in isolated islets and complete loss of glucose-stimulated insulin secretion. Four preparations of islet RNA were prepared from pools of Foxa2loxP/loxP;Ins.CRE P8 islets and hybridized with control islet RNA labeled samples on the PancChip 4.0 array using dye-swaps. The TESS program was used to identify Foxa2 sites.
Only approximately 0.3% of the genes (over 10,000 represented on PancChip 4.0) were significantly changed. Most of these have unknown biochemical functions. Three metabolic genes were identified as having altered expression in Foxa2-deleted islets and confirmed by quantitative real time PCR: Hadhsc, Argininosuccinate synthetase (Ass1), Fructose-1,6-bisphosphatase (Fbp1). A Foxa2 site was identified in intron 1 of Hadhsc and confirmed by ChIP.
Hadhsc is a direct target of Foxa2 in pancreatic beta cells. Hadhsc (schad) plays an essential role in oxidation of short chain fatty acids and it has been shown that mutations in the human gene cause persistent hyperinsulinemic hypoglycemia of infancy (PHHI).
|Platform types||Expression microarray, Expression|
Show platform Mouse PancChip
|Study Design Type||
|Study Factors||Show study factors|
|Study Assays||Show study assays|
Access to Study Data
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Last modified on Aug 02, 2011
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