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GSE21264
Mus spretus, Mus musculus, Mus musculus x mus spretus
5 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Network analysis of skin tumor progression identifies a rewired genetic architecture affecting inflammation and tumor susceptibility.
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Sex
View Samples- Mus spretus, Mus musculus, Mus musculus x mus spretus
- 4 Downloadable Samples
Description
Gene expression in self-renewing epithelial tissues is controlled by cis- and trans-activating regulatory factors that mediate responses to exogenous agents capable of causing tissue damage, infection, inflammation, or tumorigenesis. We used network construction methods to analyze the genetic architecture of gene expression in normal mouse skin in a cross between tumor-susceptible Mus musculus and tumor-resistant Mus spretus. We demonstrate that gene expression motifs representing different constituent cell types within the skin such as hair follicle cells, haematopoietic cells, and melanocytes are under separate genetic control. Motifs associated with inflammation, epidermal barrier function and proliferation are differentially regulated in mice susceptible or resistant to tumor development. The intestinal stem cell marker Lgr5 is identified as a candidate master regulator of hair follicle gene expression, and the Vitamin D receptor (Vdr) links epidermal barrier function, inflammation, and tumor susceptibility.
Publication Title
Genetic architecture of mouse skin inflammation and tumour susceptibility.
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No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
Description
Fumarylacetoacetate hydrolase (Fah), the last enzyme of the tyrosine degradation pathway, is specifically expressed in hepatocytes in the liver. Loss of Fah leads to liver failure in mice within 6-8 weeks. This can be prevented by blocking tyrosine degradation upstream of Fah with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC). Here, we investigate the impact of p21 on global gene expression in Fah deficiency.
Publication Title
Loss of p21 permits carcinogenesis from chronically damaged liver and kidney epithelial cells despite unchecked apoptosis.
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No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
Description
This study was undertaken to examine differential gene expression across the whole genome during short-term ventilator-induced lung injury in mice, a commonly used model of acute lung injury, as compared with spontaneous ventilation.
Publication Title
No associated publication
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No sample metadata fields
View Samples- Mus musculus
- 1 Downloadable Sample
Description
The oncogenic proteins expressed in human cancer cells are exceedingly difficult targets for drug discovery due to intrinsic properties of the Ras GTPase switch. As a result, recent efforts have largely focused on inhibiting Ras-regulated kinase effector cascades, particularly the Raf/MEK/ERK and PI3 kinase/Akt/mTOR pathways. We constructed murine stem cell leukemia virus (MSCV) vectors encoding oncogenic K-RasD12 with additional second site amino acid substitutions that that impair PI3 kinase/Akt or Raf/MEK/ERK activation and performed bone marrow transduction/transplantation experiments in mice. In spite of attenuated signaling properties, defective K-Ras oncoproteins induced aggressive clonal T lineage acute lymphoblastic leukemia (T-ALL). These leukemias exhibited a high frequency of somatic Notch1 mutations, which is also true of human T-ALL. Multiple independent T-ALLs restored full oncogenic Ras activity by acquiring third site mutations within the viral KrasD12 transgenes. Other leukemias with undetectable PTEN and elevated phosphoryated Akt levels showed a similar gene expression profile to human early T progenitor (ETP) T-ALL. Expressing oncoproteins that are defective for specific functions is a general strategy for assessing requirements for tumor maintenance and uncovering potential mechanisms of drug resistance in vivo. In addition, our observation that defective Kras oncogenes regain potent cancer initiating activity strongly supports simultaneously targeting distinct components of Ras signaling networks in the substantial fraction of cancers with RAS mutations.
Publication Title
No associated publication
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Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
Description
A new Treg-specific, FoxP3-GFP-hCre BAC transgenic was crossed to a conditional Dicer knock-out mouse strain to analyze the role of microRNAs (miRNA) in the development and function of regulatory T cells (Tregs). Although thymic Tregs developed normally in this setting, the cells showed evidence of altered differentiation and dysfunction in the periphery. Dicer-deficient Treg lineage cells failed to remain stable as a subset of cells down-regulated the Treg-specific transcription factor, FoxP3, while the majority expressed altered levels of multiple genes and proteins (including Neuropilin 1, GITR and CTLA-4) associated with the Treg fingerprint. In fact, a significant percentage of the Treg lineage cells took on a Th memory phenotype including increased levels of CD127, IL-4, and interferon-g. Importantly, Dicer-deficient Tregs lost suppression activity in vivo; the mice rapidly developed fatal systemic autoimmune disease resembling the FoxP3 knockout phenotype. These results support a central role for miRNAs in maintaining the stability of differentiated Treg function in vivo and homeostasis of the adaptive immune system.
Publication Title
No associated publication
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Full title: Cancer Associated Fibroblasts are activated in incipient neoplasia to orchestrate tumor promoting inflammation in an NF-B-dependent manner.
Publication Title
Cancer-Associated Fibroblasts Are Activated in Incipient Neoplasia to Orchestrate Tumor-Promoting Inflammation in an NF-kappaB-Dependent Manner.
Alternate Accession IDs
Sample Metadata Fields
Sex, Specimen part
View Samples