Comment[ArrayExpressAccession] E-GEOD-11116
Public Release Date 2011-12-23
Investigation Title ISR target genes in the liver of mock-injected and AP20187-treated mice of wildtype and Atf4-/- genotype
Comment[Submitted Name] ISR target genes in the liver of mock-injected and AP20187-treated mice of wildtype and Atf4-/- genotype
Experiment Description 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 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.
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Term Source Name EFO
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Term Source File http://www.ebi.ac.uk/efo/efo.owl
Person Last Name Oyadomari Oyadomari Harding Zhang Oyadomari Ron
Person First Name Seiichi Seiichi Heather Yuhong Miho David
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Person Email oyadomar@genome.tokushima-u.ac.jp
Person Affiliation New York University School of Medicine
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Person Address Skirball Institute, New York University School of Medicine, 540 First Avenue, New York, NY, USA
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Protocol Name P-GSE11116-1 P-GSE11116-5 P-GSE11116-4 P-GSE11116-2 P-GSE11116-3 P-GSE11116-6 P-GSE11116-7
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VALUE = normalized signal strength
SIGNAL_RAW = raw signal strength
ABS_CALL = The call in an absolute analysis that indicates whether the transcript was present (P), Absent (A), or marginal (M) Scanned using a GeneChip Scanner (Affymetrix). Microarrays were hybridized with fragmented biotinylated cRNA. Streptavidin-conjugated phycoerythrin was used for staining, followed by amplification using a biotinylated anti-streptavidin antibody. Total RNA was extracted using STAT60 (Tel-test) and RNeasy (Qiagen) following the manufacturer's protocol. Biotinylated cRNA was produced in vitro using the GeneChip labeling kit (Affymetrix). Primary image analysis of the arrays was performed using the Genechip 3.2 software (Affymetrix). The raw data from the hybridization experiments were analyzed by GeneSpring GX (Agilent Technologies). The raw signal from each gene was normalized to the mean strength of all genes from the same chip to obtain the normalized signal strength. Then, to allow visualization of all data on the same scale for subsequent analysis, the normalized signal strength of each gene was divided by the median signal strength for that gene among all samples to obtain the normalized expression level. Primary image analysis of the arrays was performed using the Genechip 3.2 software (Affymetrix). The raw data from the hybridization experiments were analyzed by GeneSpring GX (Agilent Technologies). The raw signal from each gene was normalized to the mean strength of all genes from the same chip to obtain the normalized signal strength. Then, to allow visualization of all data on the same scajavascript:ValidateSubmitForm()le for subsequent analysis, the normalized signal strength of each gene was divided by the median signal strength for that gene among all samples to obtain the normalized expression level.
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Protocol Type bioassay_data_transformation image_aquisition hybridization nucleic_acid_extraction labeling feature_extraction feature_extraction
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Publication Title Dephosphorylation of translation initiation factor 2alpha enhances glucose tolerance and attenuates hepatosteatosis in mice.
Publication Author List Oyadomari S, Harding HP, Zhang Y, Oyadomari M, Ron D
PubMed ID 18522833
Publication DOI 10.1016/j.cmet.2008.04.011
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Comment[SecondaryAccession] GSE11116
Comment[GEOLastUpdateDate] 2012-03-19
Comment[AEExperimentType] transcription profiling by array
Comment[GEOReleaseDate] 2011-12-23
Comment[ArrayExpressSubmissionDate] 2008-04-08
SDRF File E-GEOD-11116.sdrf.txt