Filters
Technology
Platform
GSE15318
Mus musculus
24 Downloadable Samples
Description
Background and Aims: In the interleukin-10-deficient (Il10-/-) mouse model of IBD, 10 quantitative trait loci (QTL) have been shown to be associated with colitis susceptibility by linkage analyses on experimental crosses of highly susceptible C3H/HeJBir (C3Bir)-Il10-/- and partially resistant C57BL/6J (B6)-Il10-/- mice. The strongest locus (C3Bir-derived cytokine deficiency-induced colitis susceptibility [Cdcs]1 on Chromosome [Chr] 3) controlled multiple colitogenic subphenotypes and contributed the vast majority to the phenotypic variance in cecum and colon. This was demonstrated by interval-specific Chr 3 congenic mice wherein defined regions of Cdcs1 from C3Bir or B6 were bred into the IL-10-deficient reciprocal background and altered the susceptible or resistant phenotype. Furthermore, this locus likely acts by inducing innate hypo- and adaptive hyperresponsiveness, associated with impaired NFB responses of macrophages. The aim of the present study was to dissect the complexity of Cdcs1 by further development and characterization of reciprocal Cdcs1 congenic strains and to identify potential candidate genes in the congenic interval. Material and Methods: In total, 15 reciprocal congenic strains were generated from Il10-/- mice of either C3H/HeJBir or C57BL/6J backgrounds by 10 cycles of backcrossing. Colitis activity was monitored by histological grading. Candidate genes were identified by fine mapping of congenic intervals, sequencing, microarray analysis and a high-throughput real-time RT-PCR approach using bone marrow-derived macrophages. Results: Within the originally identified Cdcs1-interval, three independent regions were detected that likely contain susceptibility-determining genetic factors (Cdcs1.1, Cdcs1.2, and Cdcs1.3). Combining results of candidate gene approaches revealed Fcgr1, Cnn3, Larp7, and Alpk1 as highly attractive candidate genes with polymorphisms in coding or regulatory regions and expression differences between susceptible and resistant mouse strains. Conclusions: Subcongenic analysis of the major susceptibility locus Cdcs1 on mouse chromosome 3 revealed a complex genetic structure. Candidate gene approaches revealed attractive genes within the identified regions with homologs that are located in human susceptibility regions for IBD.
Publication Title
Cdcs1 a major colitis susceptibility locus in mice; subcongenic analysis reveals genetic complexity.
Sample Metadata Fields
Sex, Specimen part
View Samples- Danio rerio
- 5 Downloadable Samples
Description
Retinoic acid (RA) and 2,3,7,8-tetrachlorodibenzo-p-dioxin activate distinct ligand-dependent transcription factors, and both cause cardiac malformation and heart failure in zebrafish embryos. We hypothesized that they cause this response by hyperactivating a common set of genes critical for heart development. To test this, we used microarrays to measure transcripts changes in hearts isolated from zebrafish embryos 1,2,4 and 12 h after exposure to 1M RA. We used hierarchical clustering to compare the transcriptional responses produced in the embryonic heart by RA and TCDD. We could identify no early responses in common between the two agents. However, at 12 h both treatments produced a dramatic downregulation of a common cluster of cell cycle progression genes, which we term the Cell Cycle Gene Cluster (CCGC). This was associated with a halt in heart growth. These results suggest that RA and TCDD ultimately trigger a common transcriptional response associated with heart failure, but not through the direct activation of a common set of genes. Among the genes rapidly induced by RA was Nr2F5, a member of the COUP-TF family of transcription repressors. We found that induction of Nr2F5 was both necessary and sufficient for the cardiotoxic response to RA.
Publication Title
Comparative genomics identifies genes mediating cardiotoxicity in the embryonic zebrafish heart.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 2 Downloadable Samples
Description
The purpose of this experiment is to understand which transcripts are differentially expressed following exposure to TCDD.
Publication Title
TCDD inhibits heart regeneration in adult zebrafish.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 7 Downloadable Samples
Description
To acquire more information regarding the local immune events during the different phases of S. aureus infection, gene profiling using microarray technology was used to identify host genes whose expression is substantively altered in the kidneys during the acute (T2) and persistent phase of infection (T28). Genes associated with the distinct transcript profiles were identified by comparing the relative abundance of transcripts at 2 days (acute) and 28 days (persistent) of infection to their abundance in the kidneys of uninfected control animals (CTL).
Publication Title
The dynamics of T cells during persistent Staphylococcus aureus infection: from antigen-reactivity to in vivo anergy.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
Description
Biliary atresia (BA) is a rare cholestatic disease of unknown etiology that affects infants and shows an incidence of 1 out of 18,000 live births in Europe (1). The first therapeutic option is a timely performed portoenterostomy. However, the majority of patients suffer from a progressive inflammatory process, which leads to complete destruction of the extra- and intrahepatic biliary system followed by end-stage liver cirrhosis. Hence, BA is the leading indication for pediatric liver transplantation worldwide (2, 3). To understand the pathogenesis of the disease and improve theoutcome of BA patients, research has focused on the inflammatory process in liver and bile ducts, in which several factors are remarkably elevated, such as activated CD4 and CD8 T-cells, TNF alpha,IFN alpha and other proinflammatory TH1 cytokines (3-8). By the time of diagnosis, however, the disease has already reached an advanced state, characterized by the complete obstruction of the extrahepatic bile ducts with impaired bile flow and fibrosis or cirrhosis of the liver. Therefore, studies in humans focusing on the trigger mechanism of BA are limited due to the paucity of liver and availability of bile duct tissue for research. One infectious animal model has been developed, in which newborn Balb/c mice exclusively show the experimental BA phenotype after infection with rhesus rotavirus (RRV) (9, 10). This model allows the analysis of the inflammatory reactions in liver and bile ducts at early steps in the development of bile duct atresia (11-20). Furthermore, inbred mouse strains have been shown to have a different susceptibility for the development of experimental BA, suggesting that Balb/c mice have an immunological gap responsible for disease progression (10, 12). The aim of this study was to identify key genes responsible for the BA phenotype by comparing the transcriptomes at an early time point after virus infection, i.e. before bile duct atresia, between two mouse strains with different susceptibilities to BA. Differences in the virus titration and the clinical course of infected mice were analyzed, and variations in the hepatic gene response assessed by comparative microarray assays were correlated to variances in the hepatic inflammatory reaction.
Publication Title
Susceptibility to experimental biliary atresia linked to different hepatic gene expression profiles in two mouse strains.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 55 Downloadable Samples
Description
[1] Lactic acidosis time course: MCF7 cells were exposed to lactic acidosis for different length of time. We used microarrays to examine the genomic programs of cells incubated under lactic acidosis for different length of time
Publication Title
Lactic acidosis triggers starvation response with paradoxical induction of TXNIP through MondoA.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus, Homo sapiens
- 7 Downloadable Samples
Description
CD95 (also called FAS and APO-1) is a prototypical death receptor that
Publication Title
CD95 promotes tumour growth.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
Description
We used gene expression microarrays to identify genes whose expression was influenced differently by TNFa in Fancc-deficient mice compared to wild type (WT) mice. To identify genes whose expression was directly or indirectly influenced by Fancc, we looked in particular for genes either suppressed or induced by TNF in WT cells that were not affected by TNF in Fancc-deficient cells.
Publication Title
FANCL ubiquitinates β-catenin and enhances its nuclear function.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The cohesin-associated protein Wapal is required for proper Polycomb-mediated gene silencing.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
Description
The cellular heterogeneity of the brain confounds efforts to elucidate the biological properties of distinct neuronal populations.
Publication Title
A translational profiling approach for the molecular characterization of CNS cell types.
Sample Metadata Fields
No sample metadata fields
View Samples