Drd2 regulates striatal gene networks.
Suppression of neuroinflammation by astrocytic dopamine D2 receptors via αB-crystallin.
Specimen part
View SamplesMyelodysplastic syndrome (MDS) is considered a disease of hematopoietic stem cell (HSC) origin. To begin to unravel the molecular mechanisms underlying the deregulation of HSCs in MDS, we performed comparative gene expression profiling on Crebbp+/- and wild type HSCs. We chose to isolate HSCs from the fetal liver (FLHSC) because at this stage there were no differences in cell number between Crebbp+/- and wild type fetal livers, suggesting no overt hematopoietic differences. Thus, any change in gene expression found in Crebbp+/- FLHSCs is likely to reflect the initially compromised genetic program of HSC regulation, as opposed to that of Crebbp+/- HSCs in adult bone marrow, where secondary changes in gene expression may also occur as compensatory mechanisms for a compromised or failing hematopoietic system. We used day 14.5 post coitus FLHSC (Sca-1+,Lin-,AA4.1+,c-Kit++) from wild type (wt) and Crebbp heterozygous (ht) embryos to examine changes in gene expression before overt myelodysplastic disease manifestation.
Mice heterozygous for CREB binding protein are hypersensitive to γ-radiation and invariably develop myelodysplastic/myeloproliferative neoplasm.
Age, Specimen part
View SamplesThe white adipose tissue (WAT) rapidly loses mass when mice are fed a diet containing trans-10, cis-12 conjugated linoleic acid (t10c12 CLA). A microarray analysis of WAT due to CLA feeding was performed to better define the processes and genes involved. WAT weight decreased by ca. 80% over 17 days of feeding a 0.5% t10c12 CLA diet. The lipid volume decreased by 90% and the number of adipocytes and total cells were reduced by15% and 47%, respectively. Microarray profiling of replicated pools of control and treated mice (n=140) at seven time points over the 17day feeding indicated between 2798 to 4318 genes showed mRNA changes of 2-fold or more. Transcript levels for genes of glucose and fatty acid import or biosynthesis were significantly reduced. A prolific inflammation response was indicated by the 2 to100-fold induction of many cytokine transcripts, including those for IL-6, IL1?, TNF ligands, and CXC family members
Trans-10, cis-12 conjugated linoleic acid causes inflammation and delipidation of white adipose tissue in mice: a microarray and histological analysis.
Age
View SamplesBackground: The ErbB3 binding protein-1 (Ebp1) belongs to a family of DNA/RNA binding proteins implicated in cell growth, apoptosis and differentiation. However, the physiological role of Ebp1 in the whole organism is not known. Therefore, we generated Ebp1-deficient mice carrying a gene trap insertion in intron 2 of the Ebp1 (pa2g4) gene.
Alterations in cell growth and signaling in ErbB3 binding protein-1 (Ebp1) deficient mice.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
CHOP induces activating transcription factor 5 (ATF5) to trigger apoptosis in response to perturbations in protein homeostasis.
Specimen part, Treatment
View SamplesThe presence of unspliced transcripts in hematopoietic stem cells (HSCs) and the proposed association of CREBBP with the constitutive production of unspliced RNA and with pre-mRNA processing prompted us to examine more closely an anomaly we had noted in microarray-based gene expression studies but had previously attributed to experimental noise. We noticed that more than half of the probe sets down-regulated in Crebbp+/- fetal liver HSCs (FLHSCs) relative to wild-type (WT) mapped entirely within introns, rather than detecting exonic or spliced sequences. We therefore set out to test whether this might be evidence that reduced CREBBP levels selectively alter the generation of full-length, unspliced pre-mRNA. We also asked whether this process might be associated with differentiation since self-renewal and lineage commitment are the both responses for which HSCs are primed.
Inactivation of a single copy of Crebbp selectively alters pre-mRNA processing in mouse hematopoietic stem cells.
Specimen part
View SamplesEnvironmental 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.
CHOP induces activating transcription factor 5 (ATF5) to trigger apoptosis in response to perturbations in protein homeostasis.
Specimen part, Treatment
View SamplesThe present study was constructed to confirm previous findings that mice on a high fat diet (HFD) treated by subcutaneous injection with exenatide (EXE) at 3g/kg once daily for 6 weeks develop exocrine pancreatic injury (Rouse et al. 2014). The present study included 12 weeks of EXE exposure at multiple concentrations (3, 10, or 30 g/kg) with multiple endpoints (histopathology evaluations, immunoassay for cytokines, immunostaining of the pancreas, serum chemistries and measurement of trypsin, amylase, and, lipase, and gene expression profiles). Time- and dose-dependent exocrine pancreatic injury was observed in mice associated with EXE exposure in a HFD environment. The time- and dose-dependent morphological changes identified in the pancreas involved acinar cell injury and death (autophagy, apoptosis, necrosis, and atrophy), cell adaptations (hypertrophy and hyperplasia), and cell survival (regeneration) accompanied with varying degrees of inflammatory response leading to secondary injury in pancreatic blood vessels, ducts, and adipose tissues. Gene expression profiles supported the presence of increased signaling for cell survival and altered lipid metabolism. The potential for EXE to cause acute or early chronic pancreatic injury was identified in a HFD environment. In human disease, the influence of pancreatitis risk factors or pre-existing chronic pancreatitis on this injury potential requires further investigation.
Extended exenatide administration enhances lipid metabolism and exacerbates pancreatic injury in mice on a high fat, high carbohydrate diet.
Sex, Specimen part
View SamplesThe goal of this experiment was to investigate the early mechanisms of human fulminant hepatitis through ConA-induced hepatitis model.Early diagnosis and interventions are important for patients with fulminant hepatitis and gene expression may be pivotal in the early diagnosis.
Genes related to the very early stage of ConA-induced fulminant hepatitis: a gene-chip-based study in a mouse model.
Sex, Specimen part, Time
View SamplesKey regulators of septum formation between the left and right ventricle in mammals, including the transcription factors TXB5 and PITX2, feature loss-of-function phenotypes that affect development of the two-chambered zebrafish heart, suggesting
Generating and evaluating a ranked candidate gene list for potential vertebrate heart field regulators.
Specimen part
View Samples