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GSE13530
Mus musculus
18 Downloadable Samples
Description
Type I interferons were discovered as the primary antiviral cytokines and are now known to serve critical functions in host defense against bacterial pathogens. Accordingly, established mediators of interferon antiviral activity may mediate previously unrecognized antibacterial functions. RNase-L is the terminal component of an RNA decay pathway that is an important mediator of interferon-induced antiviral activity. Here we identify a novel role for RNase-L in the host antibacterial response. RNase-L-/- mice exhibited a dramatic increase in mortality following
Publication Title
An essential role for the antiviral endoribonuclease, RNase-L, in antibacterial immunity.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Despite advances in investigating functional aspects of osteoblast (OB) differentiation, especially studies on how bone proteins are deposited and mineralized, there has been little research on the intracellular trafficking of bone proteins during OB differentiation. Collagen synthesis and secretion is markedly upregulated upon Ascorbic Acid (AA) stimulation. Understanding the mechanism by which collagen is mobilized in specialized OB cells is important for both basic cell biology and diseases involving defects in bone secretion and deposition. RabGTPases are major regulators on protein trafficking throughout the cell. In this study, we identified the Rab GTPases that are upregulated during 5-day AA differentiation of OBs using microarray analysis, namely Rab1, Rab3d and Rab27b.
Publication Title
Rab GTPase mediated procollagen trafficking in ascorbic acid stimulated osteoblasts.
Sample Metadata Fields
Specimen part, Cell line
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.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 14 Downloadable Samples
Description
CD38, a multi-functional membrane receptor and enzyme, consumes NAD+ to generate products such as cyclic-ADP-ribose. CD38 knockout mice show elevated tissue and blood NAD+ level. Chronic feeding of high-fat, high-sucrose diet to wild type mice leads to exercise intolerance and reduced metabolic flexibility. Loss of CD38 by genetic mutation protects mice from diet-induced metabolic deficit. These animal model results suggest that elevation of tissue NAD+ through genetic ablation of CD38 can profoundly alter energy homeostasis in animals that are maintained on a calorically-excessive Western diet.
Publication Title
Genetic Ablation of CD38 Protects against Western Diet-Induced Exercise Intolerance and Metabolic Inflexibility.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
Description
The recent identification of cancer stem cells (CSCs) in multiple human cancers provides a new inroad to understanding tumorigenesis at the cellular level. CSCs are defined by their characteristics of self-renewal, multipotentiality, and tumor initiation upon transplantation. By testing for these defining characteristics, we provide evidence for the existence of CSCs in a transgenic mouse model of glioma, S100-verbB;Trp53. In this glioma model, CSCs are enriched in the side-population (SP) cells. These SP cells have enhanced tumor-initiating capacity, self-renewal, and multipotentiality compared to non-SP cells from the same tumors. Furthermore, gene expression analysis comparing FACS-sorted cancer SP cells to non-SP cancer cells and normal neural SP cells identified 45 candidate genes that are differentially expressed in glioma stem cells. We validated the expression of two genes from this list (S100a4 and S100a6) in primary mouse gliomas and human glioma samples. Analyses of xenografted human GBM (glioblatoma multiforme) cell lines and primary human glioma tissues show that S100A4 and S100A6 are expressed in a small subset of cancer cells and that their abundance is positively correlated to tumor grade. In conclusion, this study shows that CSCs exist in a mouse glioma model, suggesting that this model can be used to study the molecular and cellular characteristics of CSCs in vivo and to further test the cancer stem cell hypothesis.
Publication Title
Cancer stem cells are enriched in the side population cells in a mouse model of glioma.
Sample Metadata Fields
No sample metadata fields
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.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 30 Downloadable Samples
Description
Murine models have been valuable instruments in defining the pathogenesis of diabetic nephropathy (DN), but they only partially recapitulate disease manifestations of human DN, limiting their utility . In order to define the molecular similarities and differences between human and murine DN, we performed a cross-species comparison of glomerular transcriptional networks. Glomerular gene expression was profiled in patients with early type 2 DN and in three mouse models (streptozotocin DBA/2 mice, db/db C57BLKS, and eNOS-deficient C57BLKS db/db mice). Species-specific transcriptional networks were generated and compared with a novel network-matching algorithm. Three shared, human-mouse cross-species glomerular transcriptional networks containing 143 (Human-STZ), 97 (Human- db/db), and 162 (Human- eNOS-/- db/db) gene nodes were generated. Shared nodes across all networks reflected established pathogenic mechanisms of diabetic complications, such as elements of JAK-STAT and VEGFR signaling pathways . In addition, novel pathways not formally associated with DN and cross-species gene nodes and pathways unique to each of the human-mouse networks were discovered. The human-mouse shared glomerular transcriptional networks will assist DN researchers in the selection of mouse models most relevant to the human disease process of interest. Moreover, they will allow identification of new pathways shared between mice and humans.
Publication Title
Identification of cross-species shared transcriptional networks of diabetic nephropathy in human and mouse glomeruli.
Sample Metadata Fields
Age, Specimen part, Disease, Disease stage, Treatment
View Samples- Mus musculus
- 215 Downloadable Samples
Description
Isoniazid induced varying degrees of hepatic steatosis in an inbred strain Mouse Diversity Panel (MDP) study. RNA was isolated from all animals for analysis of gene expression changes in the liver. The objective of this study was to identify gene expression changes that drive isoniazid-induced steatosis.
Publication Title
A systems biology approach utilizing a mouse diversity panel identifies genetic differences influencing isoniazid-induced microvesicular steatosis.
Sample Metadata Fields
Sex, Specimen part, Treatment
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.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 1 Downloadable Sample
Description
An alternative promoter of the PGC-1alpha gene gives rise to three new PGC-1alpha isoforms refered to as PGC-1a2 (A2), PGC-1a3 (A3) and PGC-1a4 (A4). The proximal PGC-1 alpha promotor transcribes the canonical PGC-1 alpha which is refered to as PGC-1a1 (A1).G1/G2/G3 samples refer to the Green fluorescent protein (GFP) control samples used in this experiment. Forced expression of the PGC-1a4 isoform results in muslce hypertrophy associated with increased IGF-1 signaling and repression of myostatin signaling.
Publication Title
A PGC-1α isoform induced by resistance training regulates skeletal muscle hypertrophy.
Sample Metadata Fields
Specimen part
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