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GSE52024
Mus musculus
8 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Prediction of miRNA-mRNA associations in Alzheimer's disease mice using network topology.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
Description
We addressed the integrated analysis of mRNA and miRNA expression levels of Tg6799 AD model mice at 4 month and 8 months of age. Total 8 gene cluster modules for co-expression network were predicted from transcriptome data and 6 modules were show relation with AD or aging. We constructed early stage AD network using data integration between mRNA and miRNA profiles and predicted miRNAs strongly involved in module regulation. We found that ARRDC3 showed AD mutation dependent changes of expression and was related metabolic dysfunction in early stage AD.
Publication Title
Prediction of miRNA-mRNA associations in Alzheimer's disease mice using network topology.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 23 Downloadable Samples
Description
Huntingtons disease (HD) involves marked early neurodegeneration in the striatum whereas the cerebellum is relatively spared despite the ubiquitous expression of full-length mutant huntingtin, implying that inherent tissue-specific differences determine susceptibility to the HD CAG mutation. To understand this tissue specificity, we compared early mutant huntingtin-induced gene expression changes in striatum to those in cerebellum in young Hdh CAG knock-in mice, prior to onset of evident pathological alterations. Endogenous levels of full-length mutant huntingtin caused qualitatively similar, but quantitatively different gene expression changes in the two brain regions. Importantly, the quantitatively different responses in striatum and cerebellum in mutant mice were well accounted for by the intrinsic molecular differences in gene expression between striatum and cerebellum in wild-type animals. Tissue-specific gene expression changes in response to the HD mutation, therefore, appear to reflect the different inherent capacities of these tissues to buffer qualitatively similar effects of mutant huntingtin. These findings highlight a role for intrinsic quantitative tissue differences in contributing to HD pathogenesis, and likely to other neurodegenerative disorders exhibiting tissue-specificity, thereby guiding the search for effective therapeutic interventions.
Publication Title
Differential effects of the Huntington's disease CAG mutation in striatum and cerebellum are quantitative not qualitative.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 6 Downloadable Samples
Description
Quantitative assays for human DNA and mRNA were used to examine the paradox that intravenously (IV) infused human multipotent stromal cells (hMSCs) can enhance tissue repair without significant engraftment. After 2 X 106 hMSCs were IV infused into mice, most of the cells were trapped as emboli in lung. The cells in lung disappeared with a half-life of about 24 hr but < 1,000 cells appeared in 6 other tissues. The hMSCs in lung up-regulated expression of multiple genes with a large increase in the anti-inflammatory protein TSG-6. After myocardial infarction, IV hMSCs but not hMSCs transduced with TSG-6 siRNA decreased inflammatory responses, reduced infarct size, and improved cardiac function. IV administration of recombinant TSG-6 also reduced inflammatory responses and reduced infarct size. The results suggest improvements in animal models and patients after IV infusions of MSCs are at least in part explained by activation of MSCs to secrete TSG-6.
Publication Title
Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6.
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 24 Downloadable Samples
Description
Huntington's disease (HD) features a unique disease-initiating mechanism hypothesized to entail an impact of the CAG repeat encoded polyglutamine region on the full-length huntingtin protein, with dominant effects that are continuous with CAG size, in a simple gain of function. To evaluate these predictions, we generated a series of heterozygous Hdh CAG knock-in mouse embryonic stem (ES) cell lines, with 18, 48, 89, 109 CAGs, and found that a continuous analytic strategy efficiently identified, from genome-wide datasets, 73 genes and 172 pathways whose expression varied continuously with CAG length. The CAG-correlated genes were distinct from the set of 754 genes that distinguished huntingtin null ES cells from wild-type controls, and CAG-correlated pathways did not display a one-to-one correspondence with the 238 pathways altered in huntingtin null ES cells. Rather, the genes that varied with CAG size were either members of the same pathways as altered genes in huntingtin null cells or were members of unique pathways related to these pathways. These findings falsified a gain of function/loss of function proposal but were consistent with the simple gain of novel function mechanism hypothesis. The dominant CAG correlated gene expression changes conformed to the genetic features of the HD initiating mechanism and were system-wide and inter-related with pathways perturbed by lack of full-length huntingtin function, urging system-wide approaches for the discovery and validation of potential modulating factors, in the search for effective HD therapeutics.
Publication Title
HD CAG-correlated gene expression changes support a simple dominant gain of function.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 65 Downloadable Samples
Description
It is widely believed that the carcinogenic action of ionizing radiation is due to targeted DNA damage and resulting mutations, but there is also substantial evidence that non-targeted radiation effects alter epithelial phenotype and the stromal microenvironment. Activation of transforming growth factor 1 (TGF) is a non-targeted radiation effect that mediates cell fate decisions following DNA damage and regulates microenvironment composition; it could either suppress or promote cancer. We asked if such non-targeted radiation effects contribute to carcinogenesis by using a novel radiation chimera model. Unirradiated Trp53 null mammary epithelium was transplanted to the mammary stroma, previously divested of endogenous epithelia, of mice previously exposed to a single low (10 -100 cGy) radiation dose. By 300 days, 100% of transplants in irradiated hosts at either 10 or 100 cGy had developed Trp53 null breast carcinomas compared to 54% in unirradiated hosts. Tumor growth rate was also increased by high, but not low, dose host irradiation. In contrast, irradiation of Tgfb1 heterozygote mice prior to transplantation failed to decrease tumor latency, or increase growth rate at any dose. Host irradiation significantly reduced the latency of invasive ductal carcinoma compared to spindle cell carcinoma. However, irradiation of either host genotype significantly increased the frequency of estrogen receptor negative tumors. These data demonstrate two concepts critical to understanding radiation risks. First, non-targeted radiation effects can significantly promote the frequency and alter the features of epithelial cancer. Second, radiation-induced TGF activity is a key mechanism of tumor promotion.
Publication Title
Radiation acts on the microenvironment to affect breast carcinogenesis by distinct mechanisms that decrease cancer latency and affect tumor type.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 1 Downloadable Sample
Description
This array set was used to identify the genes that are highly expressed in the mouse suprachiasmatic nucleus (SCN). Because pharmacological inhibition of Gai/o activity with pertussis toxin hampers intercellular synchronization and causes dampened rhythms of the entire SCN, we hypothesized that member(s) of the Regulator of G protein Signaling (RGS) family might contribute to synchronized cellular oscillations in the SCN. To test this hypothesis, we surveyed all known mouse Rgs genes for their expression by using GeneChip and selected the genes that are highly expressed in the SCN for further analysis.
Publication Title
Circadian regulation of intracellular G-protein signalling mediates intercellular synchrony and rhythmicity in the suprachiasmatic nucleus.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Treatment, Time
View Samples