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GSE29909
Mus musculus
10 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant disease caused by an alanine tract expansion mutation in Poly(A)-binding protein nuclear 1 (expPABPN1). To model OPMD in a myogenic and physiological context, we generated mouse myoblast cell clones stably expressing either human wild type (WT) or expPABPN1 at low levels. The transgene expression is induced upon myotube differentiation and results in formation of insoluble nuclear PABPN1 aggregates that are similar to the in vivo aggregates. Quantitative analysis of PABPN1 protein in myotube cultures revealed that expPABPN1 accumulation and aggregation is greater than that of the WT protein. In a comparative study we found that aggregation of expPABPN1 is more affected by inhibition of proteasome activity, as compared with the WT PABPN1 aggregation. Consistent with this, in myotubes cultures expressing expPABPN1 deregulation of the proteasome was identified as the most significantly deregulated pathway. Differences in the accumulation of soluble WT and expPABPN1 were consistent with differences in ubiquitination and protein turnover. This study indicates, for the first time, that in myotubes the ratio of soluble to insoluble expPABPN1 is significantly lower compared to that of the WT protein. We suggest that this difference can contribute to muscle weakness in OPMD.
Publication Title
Modeling oculopharyngeal muscular dystrophy in myotube cultures reveals reduced accumulation of soluble mutant PABPN1 protein.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 26 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
Oculopharyngeal muscular dystrophy (OPMD) is a late-onset progressive muscle disorder caused by a poly-alanine expansion mutation in PABPN1. The hallmark of OPMD is the accumulation of the mutant protein in insoluble nuclear inclusions. The molecular mechanisms associated with disease onset and progression are unknown. We performed a high-throughput cross-species transcriptome study of affected muscles from two OPMD animal models and from patients at pre-symptomatic and symptomatic stages. The most consistently and significantly OPMD-deregulated pathway across species is the ubiquitin-proteasome system (UPS). By analyzing expression profiles, we found that the majority of OPMD-deregulated genes are age-associated. Based on expression trends, disease onset can be separated from progression; the expression profiles of the proteasome-encoding genes are associated with onset but not with progression. In a muscle cell model, proteasome inhibition and the stimulation of immunoproteasome specifically affect the accumulation and aggregation of mutant PABPN1. We suggest that proteasome down-regulation during muscle aging triggers the accumulation of expPABPN1 that in turn enhances proteasome deregulation and leads to intranuclear inclusions (INI) formation.
Publication Title
Deregulation of the ubiquitin-proteasome system is the predominant molecular pathology in OPMD animal models and patients.
Sample Metadata Fields
Sex, Age, Disease, Disease stage
View Samples- Danio rerio
- 188 Downloadable Samples
- Affymetrix Genechip Zebrafish ST Genome Array 1.1 (zebgene11st)
Description
Zebrafish embryos have been proposed as an attractive alternative model system for hepatotoxicity testing.
Publication Title
A transcriptomics-based hepatotoxicity comparison between the zebrafish embryo and established human and rodent in vitro and in vivo models using cyclosporine A, amiodarone and acetaminophen.
Sample Metadata Fields
Compound
View Samples- Drosophila melanogaster
- 20 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Recent evidence supports a role for RNA as a common pathogenic agent in both the polyglutamine and untranslated dominant expanded repeat disorders. One feature of all repeat sequences currently associated with disease is their predicted ability to form a hairpin secondary structure at the RNA level. In order to investigate mechanisms by which hairpin forming repeat RNAs could induce neurodegeneration, we have looked for alterations in gene transcripts as hallmarks of the cellular response to toxic hairpin repeat RNAs. Three disease associated repeat sequences - CAG, CUG and AUUCU - were specifically expressed in the neurons of Drosophila and resultant common, early, transcriptional changes assessed by microarray analyses. Transcripts that encode several components of the Akt/Gsk3- signalling pathway were altered as a consequence of expression of these repeat RNAs, indicating that this pathway is a component of the neuronal response to these pathogenic RNAs and may represent an important common therapeutic target in this class of diseases.
Publication Title
Perturbation of the Akt/Gsk3-β signalling pathway is common to Drosophila expressing expanded untranslated CAG, CUG and AUUCU repeat RNAs.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Danio rerio
- 8 Downloadable Samples
IlluminaHiSeq2000
Description
We use the zebrafish embryo model to study the innate immune response against Staphylococcus epidermidis. Therefore, we injected S. epidermidis into the yolk at 2 hpf and took samples at 5 days post injection. Overall design: This deep sequence study was designed to determine the gene expression profile by Staphylococcus epidermidis infection. RNA was isolated from embryos at 5 days post injection. Wildtypes zebrafish embryos were micro-injected into the yolk (2hpf) with 20 CFU of S. epidermdis O-47 mCherry bacteria suspended in PVP (Polyvinylpyrrolidone), or Non-injected as a control. After injections embryos were transferred into fresh egg water and incubated at 28°C. At 5 days post injection 100-200 embryos per group were snap-frozen in liquid nitrogen, and total RNA was isolated using TRIZOL reagent.
Publication Title
Analysis of RNAseq datasets from a comparative infectious disease zebrafish model using GeneTiles bioinformatics.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 8 Downloadable Samples
- IlluminaHiSeq2000
Description
We use the zebrafish embryo model to study the innate immune response against Mycobacterium marinum. Therefore, we injected M. marinum into the yolk at the 64 cell stage and took samples at 5 days post injection. Overall design: This deep sequence study was designed to determine the gene expression profile by Mycobacterium marinum infection. RNA was isolated from embryos at 5 days post injection. Wildtypes zebrafish embryos were micro-injected into the yolk (64 cell stage) with 40 CFU of Mycobacterium marinum E11 mCherry bacteria suspended in PVP (Polyvinylpyrrolidone), or Non-injected as a control. After injections embryos were transferred into fresh egg water and incubated at 28°C. At 5 days post injection 50 embryos per group were snap-frozen in liquid nitrogen, and total RNA was isolated using TRIZOL reagent.
Publication Title
Analysis of RNAseq datasets from a comparative infectious disease zebrafish model using GeneTiles bioinformatics.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 3 Downloadable Samples
- IlluminaHiSeq2000
Description
We compared Agilent custom made expression microarrays with Illumina deep sequencing for RNA analysis of zebrafish embryos 5 days post fertilization, showing as expected a high degree of correlation of expression of a common set of 15,927 genes for untreated fish. The transcriptomes were also compared for fish injected in the yolk with Mycobacterium marinum Overall design: This RNA deep sequencing study was designed to determine the gene expression profile of zebrafish embryos 5 days post fertilization. We also have compared expression with embryos that were injected with Mycobacterium marinum in the yolk at 2 hours post fertilization. After injections embryos were transferred into fresh egg water and incubated at 28°C. 150 embryos of mock-injected embryos or 200 embryos injected with 12 CFU bacteria were snap-frozen in liquid nitrogen, and total RNA was isolated using TRIZOL reagent.
Publication Title
Analysis of RNAseq datasets from a comparative infectious disease zebrafish model using GeneTiles bioinformatics.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
To test the hypothesis that defects in the termination of inflammatory signaling led to skin inflammation that results in the “Itchy” phenotype, we isolated RNA from the lesional skin of Itch-/- mice and from the skin of wild-type mice and performed genome-wide mRNA expression profiling by RNA sequencing. We ranked genes based on the fold change in their expression (increased or decreased) in Itch-/- skin relative to that in wild-type skin. The expression of several TNF–induced genes were increased in Itch-/- skin, including, IL-1ß, IL-6, IL-11, IL-19, IL-1RL1, CCL4, CXCL3, CXCL2, CCL3, and CD14. Overall design: mRNA profiles comparison between wild type (WT) skin and Itch-/- mice lesional skin
Publication Title
The E3 ubiquitin ligase Itch inhibits p38α signaling and skin inflammation through the ubiquitylation of Tab1.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Enterocytes assemble dietary lipids into chylomicron particles that are taken up by intestinal lacteal vessels and peripheral tissues. Although chylomicrons are known to assemble in part within membrane secretory pathways, the modifications required for efficient vascular uptake are unknown. We report that the transcription factor Pleomorphic adenoma gene-like 2 (PLAGL2) is essential for this aspect of dietary lipid metabolism. PlagL2-/- mice die from post-natal wasting owing to failure of fat absorption. Lipids modified in the absence of PlagL2 exit from enterocytes but fail to enter interstitial lacteal vessels. Dysregulation of enterocyte genes closely linked to intracellular membrane transport identified candidate regulators of critical steps in chylomicron assembly. PlagL2 thus regulates essential and poorly understood aspects of dietary lipid absorption and its deficiency represents an authentic animal model with implications for amelioration of obesity or the metabolic syndrome.
Publication Title
Loss of the PlagL2 transcription factor affects lacteal uptake of chylomicrons.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 89 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Antimalarials have anticancer potential. Results: We have systematically tested five distinct antimalaria drugs in a panel of cancer cell lines. Conclusion: Three antimalarial classes display potent antiproliferative activity, and their potency is correlated with cancer cell gene expression patterns. Significance: We confirm and extend anticancer potential of these antimalarials and we discuss their therapeutic potential based on clinical data.
Publication Title
Anticancer properties of distinct antimalarial drug classes.
Sample Metadata Fields
Sex, Age, Cell line
View Samples