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SRP094696
Mus musculus
16 Downloadable Samples
Illumina HiSeq 2000
Description
Sporadic Creutzfeldt-Jakob disease (sCJD) is the most prevalent form of human prion disease and it is characterized by the presence of neuronal loss, spongiform degeneration, chronic inflammation and the accumulation of misfolded and pathogenic prion protein (PrPSc). The molecular mechanisms underlying these alterations are largely unknown, but the presence of intracellular neuronal calcium (Ca+2) overload, a general feature in models of prion diseases, is suggested to play a key role in prion pathogenesis. Here we describe the presence of massive regulation of Ca+2 responsive genes in sCJD brain tissue, accompanied by two Ca+2-dependent processes: endoplasmic reticulum stress and the activation of the cysteine proteases Calpains 1/2. Pathogenic Calpain activation in sCJD is linked to the cleavage of their cellular substrates, impaired autophagy and lysosomal damage, which is partially reversed by Calpain inhibition in a cellular prion model. Calpain 1 treatment enhances seeding activity of PrPSc in a prion conversion assay. Neuronal lysosomal impairment caused by Calpain over activation leads to the release of the lysosomal protease Cathepsin S that in sCJD mainly localises in axons. Additionally, massive Cathepsin S overexpression is detected in microglial cells. Alterations in Ca+2 homeostasis and activation of Calpain-Cathepsin axis already occur at pre-clinical stages of the disease as detected in a humanized sCJD mouse model. Altogether our work indicates that unbalanced Calpain-Cathepsin activation is a relevant contributor to the pathogenesis of sCJD at multiple molecular levels and a potential target for therapeutic intervention. Overall design: To identify differentially expressed genes during development of sCJD pathology we analysed the expression levels in the cortical region of tg340-PRNP129MM mice infected with sCJD MM1 brain homogenates at pre-clinical (120 dpi) and clinical (180 dpi) stages.
Publication Title
Altered Ca<sup>2+</sup> homeostasis induces Calpain-Cathepsin axis activation in sporadic Creutzfeldt-Jakob disease.
Sample Metadata Fields
Subject, Time
View Samples- Homo sapiens
- 7 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
3D cultivation of cells lead to changes in morphology of the cells. This is likely to explain the higher radioresistance of cells growing in 3D compared to cells growing in 2D cell culture.
Publication Title
Genome-wide gene expression analysis in cancer cells reveals 3D growth to affect ECM and processes associated with cell adhesion but not DNA repair.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Atherosclerosis and pressure overload are major risk factors for the development of heart failure in patients. Cardiac hypertrophy often precedes the development of heart failure. However, underlying mechanisms are incompletely understood. To investigate pathomechanisms underlying the transition from cardiac hypertrophy to heart failure we used experimental models of atherosclerosis- and pressure overload-induced cardiac hypertrophy and failure, i.e. apolipoprotein E (apoE)-deficient mice, which develop heart failure at an age of 18 months, and non-transgenic C57BL/6J (B6) mice with heart failure triggered by 6 months of pressure overload induced by abdominal aortic constriction (AAC). The development of heart failure was monitored by echocardiography, invasive hemodynamics and histology. The microarray gene expression study of cardiac genes was performed with heart tissue from failing hearts relative to hypertrophic and healthy heart tissue, respectively. The microarray study revealed that the onset of heart failure was accompanied by a strong up-regulation of cardiac lipid metabolism genes involved in fat synthesis, storage and oxidation.
Publication Title
Up-regulation of the cardiac lipid metabolism at the onset of heart failure.
Sample Metadata Fields
Age, Specimen part, Disease
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Heart failure is a leading cause of cardiovascular mortality with limited options for treatment. We used 18 month-old apolipoprotein E (apoE)- deficient mice as a model of atherosclerosis-induced heart failure to analyze whether the anti-ischemic drug ranolazine could retard the progression of heart failure. The study showed that 2 months of ranolazine treatment improved cardiac function of 18 month-old apoE-deficient mice with symptoms of heart failure as assessed by echocardiography. To identify changes in cardiac gene expression induced by treatment with ranolazine a microarray study was performed with heart tissue from failing hearts relative to ranolazine-treated and healthy control hearts. The microarray approach identified heart failure-specific genes that were normalized during treatment with the anti-ischemic drug ranolazine.
Publication Title
Up-regulation of the cardiac lipid metabolism at the onset of heart failure.
Sample Metadata Fields
Age, Specimen part, Disease, Treatment
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The human nm23-H1 was discovered as a tumor metastasis suppressor based on its reduced expression in melanoma cell lines with low versus high metastatic potential. It encodes for one of two subunits of the nucleoside-diphosphate kinase. Besides its role in the maintenance of the cells NTP pool, nm23 plays a key role in different cellular processes. The role of nm23-H1 in these processes still has to be elucidated. Our goal was to identify Nm23-H1 downstream targets by subjecting Nm23-H1 overexpressing CAL 27 cells oral squamous cell carcinoma (OSSC) to microarray analysis. The genes with changed expression patterns could be clustered into several groups: transforming growth factor (TGF) signaling pathway, cell adhesion, invasion and motility, proteasome machinery, cell-cycle, epithelial structural and related molecules and others. Based on the expression patterns observed we presume that nm23-H1 might have a role in OSSCs, which should be confirmed by future experiments.
Publication Title
Downstream targets of Nm23-H1: gene expression profiling of CAL 27 cells using DNA microarray.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Background. Nuclear factor I-A (NFI-A), a phylogenetically conserved transcription/replication protein, plays a crucial role in mouse brain development. Previous studies showed that disruption of the Nfia gene in mice leads to perinatal lethality, corpus callosum agenesis, and hydrocephalus.
Publication Title
Gene expression analysis of nuclear factor I-A deficient mice indicates delayed brain maturation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression profiling of human embryonic kidney (HEK293) cells was performed to determine the effect of high and low glucose on gene expression. Microarrays were used to identify distinct classes of genes up-regulated in HEK293 cells during cultivation for 7 days in medium with physiological (low) glucose compared to high glucose.
Publication Title
Calreticulin enhances B2 bradykinin receptor maturation and heterodimerization.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We established a novel model to assess the function of proteins under in vivo conditions. The model relies on the expansion of HEK293 cells in immunodeficient NOD.Scid mice. To validate the novel model, we performed microarray gene expression profiling of NOD.Scid-expanded HEK293 cells relative to conventionally cultivated cells. Microarray analysis revealed that cell expansion in NOD.Scid mice restored an imbalanced chaperone system without inducing a major upregulation of the entire protein folding machinery.
Publication Title
Establishment of an in vivo model facilitates B2 receptor protein maturation and heterodimerization.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Microarray gene expression profiling of aorta genes of APOE-deficient mice receiving atherosclerosis treatment with the ACE inhibitor captopril.
Publication Title
Angiotensin-converting enzyme inhibition down-regulates the pro-atherogenic chemokine receptor 9 (CCR9)-chemokine ligand 25 (CCL25) axis.
Sample Metadata Fields
Specimen part, Disease, Treatment
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
We used the microarray to investigate the lack of Tenascin-R in brain of adult and P7 mice. The aim was to find differential expressed genes which could explain the behaviour differences between the tenascin wt and ko mice. The data show that not many genes are dysregulated in the Tnr deficient mouse in comparison to the wt mouse brain.
Publication Title
Short DNA sequences inserted for gene targeting can accidentally interfere with off-target gene expression.
Sample Metadata Fields
Sex
View Samples