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GSE51650
Mus musculus
12 Downloadable Samples
Description
GDAP1 is a mitochondrial fission factor and mutations in GDAP1 cause Charcot-Marie-Tooth disease. Gdap1 knockout mice, mimicking genetic alterations of patients suffering from severe CMT forms, develop an age-related, hypomyelinating peripheral neuropathy.
Publication Title
The Gdap1 knockout mouse mechanistically links redox control to Charcot-Marie-Tooth disease.
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Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Rationale: While modulation of the serotonin transporter (5HTT) has shown to be a risk factor for pulmonary arterial hypertension for almost 40 years, there is a lack of in vivo data about the broad molecular effects of pulmonary inhibition of 5HTT. Previous studies have suggested effects on inflammation, proliferation, and vasoconstriction. The goal of this study was to determine which of these were supported by alterations in gene expression in serotonin transporter knockout mice. Methods: Eight week old normoxic mice with a 5-HTT knock-out (5HTT-/-) and their heterozygote(5HTT+/-) or wild-type(5HTT+/+) littermates had right ventricular systolic pressure(RVSP) assessed, lungs collected for RNA, pooled, and used in duplicate in Affymetrix array analysis. Representative genes were confirmed by quantitative RT-PCR and western blot. Results: RVSP was normal in all groups. Only 124 genes were reliably changed between 5HTT-/- and 5HTT+/+ mice. More than half of these were either involved in inflammatory response or muscle function and organization; in addition, some matrix, heme oxygenase, developmental, and energy metabolism genes showed altered expression. Quantitative RT-PCR for examples from each major group confirmed changes seen by array, with an intermediate level in 5HTT+/- mice. Conclusions: These results for the first time show the in vivo effects of 5HTT knockout in lungs, and show that many of the downstream mechanisms suggested by cell culture and ex vivo experiments are also operational in vivo. This suggests that the effect of 5HTT on pulmonary vascular function arises from its impact on several systems, including vasoreactivity, proliferation, and immune function.
Publication Title
Gene expression in lungs of mice lacking the 5-hydroxytryptamine transporter gene.
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No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Prion infection in animals results in neurodegeneration and eventually death. To examine the cellular impact of Prion disease, we profiled non-proliferative fully differentiated C2C12 cells, which can replicate prions to high levels. Results suggest that accumulation of high levels of PrPSc in C2C12 myotubes does not cause any overt cellular dysfunction or molecular pathology.
Publication Title
Infectious prions accumulate to high levels in non proliferative C2C12 myotubes.
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Specimen part, Cell line, Treatment, Time
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.
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Cell line, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Familial pulmonary arterial hypertension (fPAH) is associated with mutations in BMPR2. Many of these mutations occur in the BMPR2 tail domain, leaving the SMAD functions intact. In order to determine the in vivo consequences of BMPR2 tail domain mutation, we created a smooth-muscle specific doxycycline inducible BMPR2 mutation with an arginine to termination mutation at amino acid 899. When these SM22-rtTA x TetO7-BMPR2R899X mice had transgene induced for 9 weeks, starting at 4 weeks of age, they universally developed pulmonary vascular pruning as assessed by fluorescent microangiography. Approximately half the time the induced animals developed elevated right ventricular systolic pressures (RVSP), associated with extensive pruning, muscularization of small pulmonary vessels, and development of large structural pulmonary vascular changes. These lesions included large numbers of macrophages and T-cells in their adventitial compartment, as well as CD133 positive cells in the lumen. Small vessels filled with CD45 positive and sometimes CD3 positive cells were a common feature in all SM22-rtTA x TetO7-BMPR2R899X mice. Gene array experiments show changes in stress response, muscle organization and function, proliferation and apoptosis, and developmental pathways before RVSP increases. Our results show that the primary phenotypic result of BMPR2 tail domain mutation in smooth muscle is pulmonary vascular pruning leading to elevated RVSP, associated with early dysregulation in multiple pathways with clear relevance to PAH. This model should be useful to the research community in examining early molecular and physical events in the development of PAH, and as a platform to validate potential treatments.
Publication Title
Mice expressing BMPR2R899X transgene in smooth muscle develop pulmonary vascular lesions.
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No sample metadata fields
View Samples- Mus musculus
- 5 Downloadable Samples
Description
The function of ID4 in CLL development was studied in vivo using TCL1 transgenic mouse model that develop leukemia similar to human CLL. TCL1 mice with ID4 single knockout gene have accelerated CLL progression.
Publication Title
Silencing of the inhibitor of DNA binding protein 4 (ID4) contributes to the pathogenesis of mouse and human CLL.
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Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Understanding the response of memory CD8 T cells to persistent antigen re-stimulation and the role of CD4 T cell help is critical to the design of successful vaccines for chronic diseases. However, studies comparing the protective abilities and qualities of memory and nave cells have been mostly performed in acute infections, and little is known about their roles during chronic infections. Herein, we show that memory cells dominate over nave cells and are protective when present in large enough numbers to quickly reduce infection. In contrast, when infection is not rapidly reduced, memory cells are quickly lost, unlike nave cells. This loss of memory cells is due to (i) an early block in cell proliferation, (ii) selective regulation by the inhibitory receptor 2B4, and (iii) increased reliance on CD4 T cell help. These findings have important implications towards the design of T cell vaccines against chronic infections and tumors.
Publication Title
Tight regulation of memory CD8(+) T cells limits their effectiveness during sustained high viral load.
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Specimen part
View Samples- Mus musculus
- 41 Downloadable Samples
Description
Prions consist of aggregates of abnormal conformers of cellular prion protein (PrPC). They propagate by recruiting host-encoded PrPC although the critical interacting proteins and the reasons for the differences in susceptibility of distinct cell lines and populations are unknown. We derived a lineage of cell lines with markedly differing susceptibilities, unexplained by PrPC expression differences, to identify such factors. We examined the transcriptomes of prion-resistant revertants, isolated from highly susceptible cells, and identified a gene expression signature associated with susceptibility. Several of these genes encode proteins with a role in extracellular matrix (ECM) remodelling, a compartment in which disease-related PrP deposits. Loss-of-function of nine of these genes significantly increased susceptibility. Remarkably, inhibition of fibronectin 1 binding to integrin 8 by RGD peptide inhibited metalloproteinases (MMP)-2/9 whilst increasing prion propagation rates. This indicates that prion replication may be controlled by MMPs at the ECM in an integrin-dependent manner.
Publication Title
Identification of a gene regulatory network associated with prion replication.
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Treatment
View Samples- Mus musculus
- 19 Downloadable Samples
Description
We isolated fetal murine urogenital sinus epithelium and urogenital sinus mesenchyme and determined their global gene expression profiles to define their differentially expressed regulators. To distinguish gene expression patterns that are shared by other developing epithelial/mesenchymal compartments in the embryo from those that pertain to the prostate stem cell niche, we also determine the global gene expression of epidermis and dermis of the same embryos. We identified a distinctive core of transcripts that were differentially regulated in the prostate stem cell niche. Our analysis indicates that several of the key transcriptional components that are likely to be active in the embryonic prostate stem cell niche regulate processes such as self-renewal (e.g., E2f and Ap2), lipid metabolism (e.g., Serbp1) and cell migration (e.g., Areb6 and Rreb1). Several of the promoter binding motifs that are enriched in the profiles are shared between the prostate epithelial/mesenchymal compartments and their epidermis/dermis counterparts, indicating their likely relevance in epithelial/mesenchymal signaling in primitive cellular compartments. We also focused on defining ligand-receptor interactions that may be relevant in controlling signals in the stem cell niche and identified the Wnt/beta-catenin, ephrin, Notch, sonic hedgehog, FGF, TGF-beta and bone morphogenic signaling pathways as being of likely relevance in the prostate stem cell niches. Members of the integrins family including those that bind extracellular matrix proteins such as laminin and activate latent TGF-beta are also expressed in the prostate niche.development.
Publication Title
Molecular signatures of the primitive prostate stem cell niche reveal novel mesenchymal-epithelial signaling pathways.
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Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
Description
BMPR2 mutation causes pulmonary arterial hypertension (PAH); ACE2 treatment can resolve established BMPR2-mediated PAH. The purpose of this study was to uncover the molecular mechanism behind this.
Publication Title
Cytoskeletal defects in Bmpr2-associated pulmonary arterial hypertension.
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Sex, Specimen part, Treatment
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