8-12 week old Pdx1+/- vs Pdx1+/+ mouse littermates - Study GBCO3975
Genomics Study Specifications
|Study Name||8-12 week old Pdx1+/- vs Pdx1+/+ mouse littermates|
|Contact Name||David Groff (University of Pennsylvania)|
|My Strategies||Return to My Strategies page|
|Classification||Islet/beta-cell stimulation/injury; Cell stimulation/injury; Targets and roles of transcriptional regulators|
|BCBC Release Date||July 21, 2010|
|Public Release Date||July 21, 2010|
|Citation||Sachdeva MM, Claiborn KC, Khoo C, Yang J, Groff DN, Mirmira RG, Stoffers DA. Pdx1 (MODY4) regulates pancreatic beta cell susceptibility to ER stress. Proc Natl Acad Sci U S A. 2009. 106:19090-5|
The aim of this experiment was to use global gene expression profiling to identify genes that are differentially expressed in the islets from Pdx1+/- mice compared to islets isolated from Pdx1 +/+ littermates. The Pdx1 null mutation consists of a nuclear targeted _-galactosidase cassette fused in-frame with the N terminus of PDX-1.
Identify Pdx1 transcriptional targets involved in ER function as part of a larger study to define the role of Pdx1 in compensatory beta cell mass expansion that occurs in the progression to type 2 diabetes in humans.
Gene expression in islets isolated from 8- to 12-week-old Pdx1+/- and Pdx1+/+ littermates were examined using the Mouse PancChip 6.1 platform.
An overlap analysis comparing the effects of acute and chronic Pdx1 deficiency on gene expression in Min6 cells and primary islets resulted in a short list of commonly dysregulated genes. The eight genes down-regulated include the known Pdx1 targets Mafa, Slc2a2 (also known as Glut2), and Pax4. Two of the five remaining genes, Ero1lb and Nnat, encode ER resident proteins implicated in ER stress responses whose differential expression were also observed in AdshPdx1-infected Min6 cells.
Pdx1 regulates a broad array of genes involved in diverse functions of the ER, including proper disulfide bond formation, protein folding, and the unfolded protein response. These findings suggest that Pdx1 deficiency leads to a failure of beta cell compensation for insulin resistance at least in part by impairing critical functions of the ER.
|Platform types||Expression, Expression microarray|
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 Jan 17, 2012
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