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GSE26671
Mus musculus
12 Downloadable Samples
Description
An initial cellular change in the pathogenesis of heart failure is cardiomyocyte hypertrophy, characterized by increased cell size, enhanced protein synthesis and reactivation of fetal genes. In addition to mechanical stresses, several neurohumoral factors have been identified as potent hypertrophic agents, including angiotensin II, endothelin, and catecholamines.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
Description
Activation of the Sonic hedgehog (Shh) signaling pathway due to Patched 1 (PTCH1) mutation is a key event in sporadic and familial basal cell carcinoma (BCC) development. To find out the specific pathway for therapeutic intervention, we developed a mouse BCC model by skin specific Ptch1 inactivation, and sought to identify novel Shh targets.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 2 Downloadable Samples
Description
To identify p45 target genes, we conducted gene expression profiling with p45-null megakaryocytes cultured from E14.5 fetal liver. Many genes encoding membrane proteins and enzymes related to platelet function, including Txas, Glycoprotein 6 (Gp6) and Selectin P (Selp), were repressed in the absence of p45. Considering the similar DNA binding specificity of p45 and Nrf2 in vitro, we expected p45 to activate cytoprotective genes that are established Nrf2 targets. However, the expression of numerous detoxifying enzymes and stress-responsive genes, including NAD(P)H:quinone oxidoreductase (Nqo1), were increased in the absence of p45.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 38 Downloadable Samples
Description
Germ free (GF) and conventionalized (CONV-D) wild-type C57Bl/6 male mice in the CARB-fed, 24h fasted, and 30d trained states; plus GF and CONV-D CARB-fed Ppara-/- mice. CARB-fed indicates a standard polysaccharide-rich mouse chow diet.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 22 Downloadable Samples
Description
Susceptible and Resistant mouse strain, e.g. DBA/2J and C57BL/6J respectively, were inoculated with a highly pathogenic H5N1 influenza A virus (A/Hong Kong/213/2003) for 72 hours.
Publication Title
Host genetic variation affects resistance to infection with a highly pathogenic H5N1 influenza A virus in mice.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 14 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
CHOP induces activating transcription factor 5 (ATF5) to trigger apoptosis in response to perturbations in protein homeostasis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 21 Downloadable Samples
Description
Disruption of protein folding in the endoplasmic reticulum triggers the Unfolded Protein Response (UPR), a transcriptional and translational control network designed to restore protein homeostasis. Central to the UPR is PERK phosphorylation of the alpha subunit of eIF2 (eIF2~P), which represses global translation coincident with preferential translation of mRNAs, such as ATF4 and CHOP, that serve to implement the UPR transcriptional regulation. In this study, we used sucrose gradient ultracentrifugation and a genome-wide microarray approach to measure changes in mRNA translation during ER stress. Our analysis suggests that translational efficiencies vary across a broad range during ER stress, with the majority of transcripts being either repressed or resistant to eIF2~P, while a notable cohort of key regulators are subject to preferential translation. From this latter group, we identify IBTKa as being subject to both translation and transcriptional induction during eIF2~P in both cell lines and a mouse model of ER stress. Translational regulation of IBTKalpha mRNA involves the stress-induced relief of two inhibitory uORFs in the 5'-leader of the transcript. Depletion of IBTKalpha by shRNA reduced viability of cultured cells coincident with increased caspase 3/7 cleavage, suggesting that IBTKalpha is a key regulator in determining cell fate during the UPR.
Publication Title
Selective mRNA translation during eIF2 phosphorylation induces expression of IBTKα.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
Description
Analysis of gene expression in lungs of C57BL/6J mice that develop chronic airway disease phenotypes after a single Sendai virus infection, compared with mice treated with UV-inactivated virus.
Publication Title
Persistent activation of an innate immune response translates respiratory viral infection into chronic lung disease.
Sample Metadata Fields
Sex, Time
View Samples- Mus musculus
- 18 Downloadable Samples
Description
HD R6/1 transgenic mouse line brain hemispheres dissected. RNA targets were created for transgenics and wildtypes at time points 18, 22 and 27 weeks. Profiles and data analysis performed using the Bioconductor software and linear model contrasts using LIMMA on RMA probeset summarys.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 14 Downloadable Samples
Description
Environmental stresses that disrupt protein homeostasis induce phosphorylation of eIF2, triggering repression of global protein synthesis coincident with preferential translation of ATF4, a transcriptional activator of the Integrated stress response (ISR). Depending on the extent of protein disruption, ATF4 may not be able to restore proteostatic control and instead switch to a terminal outcome that features elevated expression of the transcription factor CHOP (GADD153/DDIT3). The focus of this study was to define the mechanisms by which CHOP directs gene regulatory networks that determine cell fate. We find that in response to proteasome inhibition, CHOP induces the expression of a collection of genes encoding transcription regulators, including ATF5, which is preferentially translated during eIF2 phosphorylation. Transcriptional expression of ATF5 is directly activated by both CHOP and ATF4. Knock-down of ATF5 increased cell survival in response to proteasome inhibition, supporting the idea that both ATF5 and CHOP have pro-apoptotic functions. Transcriptome analyses of ATF5-dependent genes revealed targets involved in apoptosis, including, NOXA, which is important for inducing cell death during proteasome inhibition. This study suggests that the ISR features a feed-forward loop of stress induced transcriptional regulators, each subject to transcriptional and translational control that can switch cell fate towards apoptosis.
Publication Title
CHOP induces activating transcription factor 5 (ATF5) to trigger apoptosis in response to perturbations in protein homeostasis.
Sample Metadata Fields
Specimen part, Treatment
View Samples