Filters
Technology
Platform
GSE16994
Mus musculus
8 Downloadable Samples
Description
Several ocular diseases involve the iris, notably including oculocutaneous albinism, pigment dispersion syndrome, and exfoliation syndrome. To screen for candidate genes that may be active in these diseases, genome-wide iris gene expression patterns were comparatively analyzed from mouse models of these conditions.
Publication Title
Microarray analysis of iris gene expression in mice with mutations influencing pigmentation.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
Description
BMP4 is down-regulated in metastatic human and murine mammary tumours. Here we determined the effect of ectopic mouse Bmp4 re-expression on global gene expression patterns in orthotopic primary mammary tumours in syngeneic Balb/c mice.
Publication Title
BMP4 inhibits breast cancer metastasis by blocking myeloid-derived suppressor cell activity.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Description
To identify the precise molecular mechanisms that could contribute to the increase in colon carcinogenesis, microarray gene expression analysis was performed on colon RNA isolated from 5-week-old VhlF/F and VhlIE, VhlIE/Apcmin/+ and VhlF/F/Apcmin/+ mice.
Publication Title
Hypoxia-inducible factor-2α activation promotes colorectal cancer progression by dysregulating iron homeostasis.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
Description
Comparison of transcriptional profile of CD8 cytotoxic T lymphocytes terated with the mTORC1 inhibitor rapamycin or the mTOR inhibitor KU-0063794 and comparison with proteomic analysis.
Publication Title
The cytotoxic T cell proteome and its shaping by the kinase mTOR.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 57 Downloadable Samples
Description
To gain insight into the changes in gene expression pattern upon Ebola infection, CD45+/+ (100% protein level) and CD45+/- (62% protein level) mice were challenged with mouse adapted Ebola virus. At time-points day 0, 1, 3, 5, 7, 9, 11 and 13, spleen tissue was harvested and splenocytes isolated. Total RNA was isolated for mRNA expression analysis. The mouse genome 430 2.0 array (Affymetrix, Inc.), which consists of over 39,000 genes in a single array, was used. Based on gene expression patterns, the variable genes were grouped into sixteen clusters. Each cluster contained genes associated with cellular immune processes, signaling, cell-cycle, complement coagulation cascade, biosynthesis/metabolism, ubiquitous genes involved in several cascades, and genes of unknown function. Interestingly, gene expression in clusters 2 and 3 were significantly downregulated by day 1 following EBOV challenge in CD45100% mice. In contrast, at day 1 following EBOV infection, the CD45 62% mice maintained gene expression patterns similar to day 0. The differences in gene expression patterns between the CD45 100% and CD45 62% splenocytes were less apparent at day 3 following infection and by days 5 and 7 they became very similar. At day 9, when wild-type mice had succumbed to the disease, the pattern in CD45 62% mice remained similar to the day 7 patterns of CD45 100% and CD45 62% mice. The pattern at days 11 and 13 in the CD45 62% mice had returned to that of day 0 CD45 100% or CD45 62% mice. These results suggested that in CD45 100% mice, subversion of the cell transcriptional machinery during the early stages of EBOV infection (day 1) might represent a major factor leading to death of the mice. In CD45 62% mice, early control of gene regulation likely provided the appropriate antiviral responses leading to regulated inflammation, immune co-stimulation, and survival.
Publication Title
Reduced levels of protein tyrosine phosphatase CD45 protect mice from the lethal effects of Ebola virus infection.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Skin and bladder epithelia form effective permeability barriers through the activation of distinct differentiation gene programs. Employing a genome-wide gene expression study, we identified transcription regulators whose expression correlates highly with that of differentiation markers both in bladder and skin, including the Grainyhead factor Get1/Grhl3, already known to be important for epidermal barrier formation. In the bladder, Get1 is most highly expressed in the differentiated umbrella cells and its mutation in mice leads to a defective bladder epithelial barrier formation due to failure of apical membrane specialization. Genes encoding components of the specialized urothelial membrane, the uroplakins, were downregulated in Get1-/- mice. At least one of these genes, Uroplakin II, is a direct target of Get1. The urothelial-specific activation of the Uroplakin II gene is due to selective binding of Get1 to the Uroplakin II promoter in urothelial cells, most likely regulated by histone modifications. These results demonstrate a key role for Get1 in urothelial differentiation and barrier formation.
Publication Title
The epidermal differentiation-associated Grainyhead gene Get1/Grhl3 also regulates urothelial differentiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Skin and bladder epithelia form effective permeability barriers through the activation of distinct differentiation gene programs. Employing a genome-wide gene expression study, we identified transcription regulators whose expression correlates highly with that of differentiation markers both in bladder and skin, including the Grainyhead factor Get1/Grhl3, already known to be important for epidermal barrier formation. In the bladder, Get1 is most highly expressed in the differentiated umbrella cells and its mutation in mice leads to a defective bladder epithelial barrier formation due to failure of apical membrane specialization. Genes encoding components of the specialized urothelial membrane, the uroplakins, were downregulated in Get1-/- mice. At least one of these genes, Uroplakin II, is a direct target of Get1. The urothelial-specific activation of the Uroplakin II gene is due to selective binding of Get1 to the Uroplakin II promoter in urothelial cells, most likely regulated by histone modifications. These results demonstrate a key role for Get1 in urothelial differentiation and barrier formation.
Publication Title
The epidermal differentiation-associated Grainyhead gene Get1/Grhl3 also regulates urothelial differentiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 51 Downloadable Samples
Description
To characterize genes, pathways, and transcriptional regulators enriched in the mouse cornea, we compared the expression profiles of whole mouse cornea, bladder, esophagus, lung, proximal small intestine, skin, stomach, and trachea.
Publication Title
The Ets transcription factor EHF as a regulator of cornea epithelial cell identity.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 190 Downloadable Samples
Description
The process for evaluating chemical safety is inefficient, costly, and animal intensive. There is growing consensus that the current process of safety testing needs to be significantly altered to improve efficiency and reduce the number of untested chemicals. In this study, the use of short-term gene expression profiles was evaluated for predicting the increased incidence of mouse lung tumors. Animals were exposed to a total of 26 diverse chemicals with matched vehicle controls over a period of three years. Upon completion, significant batch-related effects were observed. Adjustment for batch effects significantly improved the ability to predict increased lung tumor incidence. For the best statistical model, the estimated predictive accuracy under honest five-fold cross-validation was 79.3% with a sensitivity and specificity of 71.4 and 86.3%, respectively. A learning curve analysis demonstrated that gains in model performance reached a plateau at 25 chemicals, indicating that the size of the current data set was sufficient to provide a robust classifier. The classification results showed a small subset of chemicals contributed disproportionately to the misclassification rate. For these chemicals, the misclassification was more closely associated with genotoxicity status than efficacy in the original bioassay. Statistical models were also used to predict dose-response increases in tumor incidence for methylene chloride and naphthalene. The average posterior probabilities for the top models matched the results from the bioassay for methylene chloride. For naphthalene, the average posterior probabilities for the top models over-predicted the tumor response, but the variability in predictions were significantly higher. The study provides both a set of gene expression biomarkers for predicting chemically-induced mouse lung tumors as well as a broad assessment of important experimental and analysis criteria for developing microarray-based predictors of safety-related endpoints.
Publication Title
Use of short-term transcriptional profiles to assess the long-term cancer-related safety of environmental and industrial chemicals.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Breast cancer metastasis to bone is a critical determinant of long-term survival after treatment of primary tumors. We used a mouse model of spontaneous bone metastasis to determine new molecular mechanisms. Differential transcriptome comparisons of primary and metastatic tumor cells revealed that a substantial set of genes suppressed in bone metastases were highly enriched for promoter elements for the type I interferon (IFN) regulatory factor, Irf7, itself suppressed in mouse and human metastases. The critical function of the Irf7 pathway was demonstrated by restoration of exogenous Irf7 or systemic interferon administration, which significantly reduced bone metastases and prolonged metastasis-free survival. Using mice deficient in the type I receptor (Ifnar1-/-) or mature B, T and NK cell responses (NOD Scid IL-2r-/- mice), we demonstrated that Irf7-driven suppression of metastasis was reliant on IFN signaling to host immune cells. Metastasis suppression correlated with decreased accumulation of myeloid-derived suppressor cells and increased CD4++, CD8 T cells and NK cells in the peripheral blood and was reversed by depletion of CD8+ cells and NK cells. Clinical importance of our findings was demonstrated as increased primary tumor Irf7 expression predicted prolonged bone and lung metastasis-free survival. Thus we report for the first time, a novel innate immune pathway, intrinsic to breast cancer cells, whose suppression in turn restricts systemic immunosurveillance to enable metastasis. This pathway may constitute a novel therapeutic target for restricting breast cancer metastases.
Publication Title
Silencing of Irf7 pathways in breast cancer cells promotes bone metastasis through immune escape.
Sample Metadata Fields
Specimen part
View Samples