Transcription profiling of mice with hromosome substitution from A/J strain vs parental strains, and acute lung injury following ozone exposure
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: George Leikauf
PROVIDER: E-MEXP-17 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Alzheimer’s disease (AD) is a major neurodegenerative disease characterized by extracellular amyloid β (Aβ) plaques and intracellular hyperphosphorylated tau (P-tau). Increasing evidence indicates that extracellular vesicles (EVs) play an important role in AD pathogenesis. We previously reported that the choroid plexus epithelial (CPE) cells, present at the interface between blood and cerebrospinal fluid (CSF), show increased secretion of EVs into the CSF in response to peripheral inflammation. Here, we studied the importance of CP-derived EVs in AD pathogenesis. We observed increased EV levels in the CSF of 7 weeks old transgenic APP/PS1 mice, correlating with higher Aβ CSF levels at this age, while levels normalized with age. To study whether the elevated Aβ CSF levels might be responsible for this increase, mice were intracerebroventricularly (icv) injected with Aβ oligomers (AβO) which revealed a significant increase in the amount of CD9 and CD81 positive EVs in the CSF. The importance of the CPE cells as EV source was shown by in vitro analysis of AβO stimulated primary CPE cells and in vivo analysis of the CP by transmission electron microscopy (TEM). Evaluation of EV marker immunostaining, both from AβO icv injected mice and APP/PS1 mice, confirmed the upregulation of EV biogenesis in the CP. Interestingly, AβO-induced, CP-derived EVs induced pro-inflammatory effects in mixed cortical cultures (MCC) whereas proteome analysis revealed the presence of complement protein C3, amongst other inflammatory proteins. Additionally, we could show for the first time that AβO induce an upregulation of C3 in CPE cells. These data highlight the CP and CP-derived, C3-containing EVs as novel players in the emerging importance of the complement pathway in the pathogenesis of AD. Strikingly, inhibition of EV production using GW4869 resulted in protection against the AβO-induced cognitive decline. In conclusion, our results show that intraventricular AβO induce both C3 activation and EV secretion by the CP and that these EVs contain pro-inflammatory molecules, including C3, which play a role in neuroinflammation and loss of cognition. This suggests that inhibition of EV production by the CP might be an interesting therapeutic approach to be explored in the prevention or treatment of AD.
2021-09-09 | PXD021665 | Pride
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2016-07-25 | E-GEOD-67680 | biostudies-arrayexpress
Project description:Diurnal oscillations of gene expression controlled by the circadian clock underlie rhythmic physiology across most living organisms. Although such rhythms have been extensively studied at the level of transcription and mRNA accumulation, little is known about the accumulation patterns of proteins. Here, we quantified temporal profiles in the murine hepatic proteome under physiological light–dark conditions using stable isotope labeling by amino acids quantitative MS. To measure the daily accumulation of proteins, we designed an SILAC MS experiment, in which total protein extracts were harvested from C57BL/6J mice every 3 h for 2 d (eight samples per day). Relative protein abundance in each of 16 samples was quantified against a common reference sample labeled using the SILAC method. The generated mass spectra allowed the identification of a total of 5,827 distinct proteins, of which 70% yielded relative measurements in at least 8 of 16 samples. Our analysis identified over 5,000 proteins, of which several hundred showed robust diurnal oscillations with peak phases enriched in the morning and during the night and related to core hepatic physiological functions. Combined mathematical modeling of temporal protein and mRNA profiles indicated that proteins accumulate with reduced amplitudes and significant delays, consistent with protein half-life data. Moreover, a group comprising about one-half of the rhythmic proteins showed no corresponding rhythmic mRNAs, indicating significant translational or posttranslational diurnal control. Such rhythms were highly enriched in secreted proteins accumulating tightly during the night. Also, these rhythms persisted in clock-deficient animals subjected to rhythmic feeding, suggesting that food-related entrainment signals influence rhythms in circulating plasma factors
2014-08-08 | PXD001211 | Pride
Project description:Heart failure is a leading cause of cardiovascular mortality with limited options for treatment. We analyzed whether the anti-ischemic drug ranolazine could retard the progression of heart failure in an experimental model of heart failure induced by 6 months of chronic pressure overload. The study showed that 2 months of ranolazine treatment improved cardiac function of aortic constricted C57BL/6J (B6) mice with symptoms of heart failure as assessed by echocardiography. The microarray gene expression study of heart tissue from failing hearts relative to ranolazine-treated and healthy control hearts identified heart failure-specific genes that were normalized during treatment with the anti-ischemic drug ranolazine. Microarray gene expression profiling was performed with heart tissue isolated from three study groups: (i) untreated 10 month-old C57BL/6J (B6) mice with heart failure induced by 6 months of abdominal aortic constriction (AAC), (ii) 10 month-old B6 mice with 6 months of AAC and two months of treatment with the anti-ischemic drug ranolazine (200 mg/kg), and (iii) age-matched, untreated, sham-operated B6 control mice.
2010-12-03 | E-GEOD-25766 | biostudies-arrayexpress
Project description:Heart failure is a leading cause of cardiovascular mortality with limited options for treatment. We used 18 month-old apolipoprotein E (apoE)- deficient mice as a model of atherosclerosis-induced heart failure to analyze whether the anti-ischemic drug ranolazine could retard the progression of heart failure. The study showed that 2 months of ranolazine treatment improved cardiac function of 18 month-old apoE-deficient mice with symptoms of heart failure as assessed by echocardiography. To identify changes in cardiac gene expression induced by treatment with ranolazine a microarray study was performed with heart tissue from failing hearts relative to ranolazine-treated and healthy control hearts. The microarray approach identified heart failure-specific genes that were normalized during treatment with the anti-ischemic drug ranolazine. Microarray gene expression profiling was performed with heart tissue isolated from (i) untreated 18 month-old apoE-deficient mice with heart failure relative to (ii) 18 month-old apoE-deficient mice treated for two months with the anti-ischemic drug ranolazine (200 mg/kg), and (iii) age-matched non-transgenic C57BL/6J (B6) control mice.
2010-12-03 | E-GEOD-25767 | biostudies-arrayexpress
Project description:B6 mice have been infected via the aerosol route with a low-dose (100 CFUs)of Mycobacterium tuberculosis for 30 days and 70 days.<br><br>Uninfected mice have been used as experimental controls.
2008-12-17 | E-MEXP-1899 | biostudies-arrayexpress
Project description:Compare miRNA expression profiles in epididymal adipocytes from control and diet-induced obese (DIO) mice
2009-02-25 | E-MEXP-1932 | biostudies-arrayexpress
Project description:Compare miRNA expression profiles in epididymal adipocytes from normal and leptin deficient obese mice
2009-02-21 | E-MEXP-1789 | biostudies-arrayexpress
Project description:Despite considerable progress understanding genes that affect the HDL particle, its function, and cholesterol content, genes identified to date explain only a small percentage of the genetic variation. We used N-ethyl-N-nitrosourea mutagenesis in mice to discover novel genes that affect HDL cholesterol levels. Two mutant lines (Hlb218 and Hlb320) with low HDL cholesterol levels were established. Causal mutations in these lines were mapped using linkage analysis: For line Hlb218 within a 12 Mbp region on Chr 10; and for line Hlb320 within a 17 Mbp region on Chr 7. High-throughput sequencing of Hlb218 liver RNA identified a mutation in Pla2g12b. The transition of G to A leads to a cysteine to tyrosine change and most likely causes a loss of a disulfide bridge. Microarray analysis of Hlb320 liver RNA showed a 7-fold downregulation of Hpn; sequencing identified a mutation in the 3M-bM-^@M-2 splice site of exon 8. Northern blot confirmed lower mRNA expression level in Hlb320 and did not show a difference in splicing, suggesting that the mutation only affects the splicing rate. In addition to affecting HDL cholesterol, the mutated genes also lead to reduction in serum non-HDL cholesterol and triglyceride levels. Despite low HDL cholesterol levels, the mice from both mutant lines show similar atherosclerotic lesion sizes compared to control mice. These new mutant mouse models are valuable tools to further study the role of these genes, their affect on HDL cholesterol levels, and metabolism. Mutant mice were generated as part of The Jackson LaboratoryM-bM-^@M-^Ys Heart, Lung, Blood, and Sleep Disorder Mutagenesis Program by treating male C57BL/6J (B6) mice with N-ethyl-N-nitrosourea (ENU). Third generation (G3) mice were phenotyped to ensure capture of both dominant and recessive mutations. Two unique G3 animals with low HDL cholesterol levels were then used to establish new inbred lines (Hlb218 and Hlb320) by mating them with B6 mice and intercrossing the offspring with low HDL cholesterol for 7 generations. Livers from 3 Hlb218, 3 Hlb320 males, and 6 B6 male controls were obtained for gene expression analysis. The samples were randomized over Illumina Mouse-6 Expression 1.1 BeadChips .
2012-06-30 | E-GEOD-37902 | biostudies-arrayexpress
Project description:We sought to characterize the persistnet changes in brain miRNAs across multiple mouse models of fetal alcohol exposure We used miRNA expression arrays to characterize and observe the deregulation of brain specific ncRNAs Whole brain tissue was harvested from day 70 fetal alcohol exposed males and matched controls for RNA extraction and hybridization to affymetrix miRNA 2.0 arrays. We obtained tissue from four models: Trimiester 1,2, and 3, injections and contious preference drinking.
2011-12-14 | E-GEOD-34413 | biostudies-arrayexpress