Project description:To identify the target genes of integrated stress reponse (ISR), we have employed whole genome microarray expression in MEF cells. ISR gene setimation under ER stress condition using Perk -/-, Atf4 -/-, eIF2a S51A mutant, Fv2E-PERK MEF cells
Project description:To identify the target genes of integrated stress reponse (ISR) in WAT and BAT, we have employed whole genome microarray expression in WAT and BAT specific Fv2E-PERK transgenic mice. The mAP::Fv2E-PERK transgenic mice were injected by AP20187 or mock.
Project description:To identify the target genes of integrated stress reponse (ISR) in skeletal muscle, we have employed whole genome microarray expression in muscle specific Fv2E-PERK transgenic mice and C2C12 myotubes expressed in Fv2E-PERK. As a result, we identified that Fgf21 mRNA expression was commonly induced in skeletal muscle and C2C12.
Project description:To identify the target genes of integrated stress reponse (ISR) in adipose tissue, we have employed whole genome microarray expression in adipose specific Fv2E-PERK transgenic mice.
Project description:To identify the target genes of integrated stress reponse (ISR) in WAT and BAT, we have employed whole genome microarray expression in WAT and BAT specific Fv2E-PERK transgenic mice.
Project 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 2alpha (eIF2a)-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(aP) correlated with lower expression of the adipogenic nuclear receptor PPARgamma and its upstream regulators, the transcription factors C/EBPalpha and C/EBPbeta, in transgenic mouse liver, whereas eIF2alpha phosphorylation promoted C/EBP translation in cultured cells and primary hepatocytes. These observations suggest that eIF2(aP)-mediated translation of key hepatic transcriptional regulators of intermediary metabolism contributes to the detrimental consequences of nutrient excess. Keywords: genotype comparison The high expressing Ttr::Fv2E-Perk transgenic mice was injected by either mock or AP20187. Wildtype and Alb::GC transgenic mice were fed by either Low Fat Diet (LFD) or High Fat Diet (HFD) . 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.
Project description:Comparison of genes induced during activation of the Integrated Stress Response by tunicamycin or following AP20187 induced dimerization of a Fv2E-PERK chimera in wildtype cells and cells carrying mutations in key ISR signaling molecules.
