Transcriptomics

Dataset Information

47

ISR target genes in the liver of mock-injected and AP20187-treated mice of wildtype and Atf4-/- genotype


ABSTRACT: The molecular mechanisms linking the stress of unfolded proteins in the endoplasmic reticulum (ER stress) to glucose intolerance in obese animals are poorly understood. In this study enforced expression of a translation initiation 2α (eIF2α)-specific phosphatase, GADD34, was used to selectively compromise signaling in the eIF2(αP)-dependent arm of the ER unfolded protein response in liver of transgenic mice. The transgene resulted in lower liver glycogen levels and susceptibility to fasting hypoglycemia in lean mice and glucose tolerance and diminished hepato-steatosis in animals fed a high fat diet. Attenuated eIF2(αP) correlated with lower expression of the adipogenic nuclear receptor PPARγ and its upstream regulators, the transcription factors C/EBPα and C/EBPβ, in transgenic mouse liver, whereas eIF2α phosphorylation promoted C/EBP translation in cultured cells and primary hepatocytes. These observations suggest that eIF2(αP)-mediated translation of key hepatic transcriptional regulators of intermediary metabolism contributes to the detrimental consequences of nutrient excess. Keywords: genotype comparison Overall design: The low expressing Ttr::Fv2E-Perk transgene (#58) was bred into the Atf4 knockout strain and the derivative compound heterozygous mice (in the mixed FvB/n; Swiss Webster background) were backcrossed to the Atf4+/- parental stock and Ttr::Fv2E-PERK positive siblings with Atf4+/+ and Atf4-/- genetypes were analyzed.

INSTRUMENT(S): [MG_U74Av2] Affymetrix Murine Genome U74A Version 2 Array

ORGANISM(S): Mus musculus  

SUBMITTER: Seiichi Oyadomari  

PROVIDER: GSE11116 | GEO | 2011-12-23

SECONDARY ACCESSION(S): PRJNA107011

REPOSITORIES: GEO

Similar Datasets

2011-12-23 | E-GEOD-11116 | ArrayExpress
| GSE11210 | GEO
2011-12-23 | E-GEOD-11210 | ArrayExpress
2012-01-20 | E-GEOD-29929 | ArrayExpress
2016-07-03 | E-GEOD-68265 | ArrayExpress
2014-06-02 | E-GEOD-54581 | ArrayExpress
2009-11-10 | GSE11684 | GEO
2009-11-23 | E-GEOD-11684 | ArrayExpress
| GSE40826 | GEO
2009-11-23 | E-GEOD-11685 | ArrayExpress