Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA292136 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Allergic Airway Disease is Dependent on Methylene-Tetrahydrofolate Reductase (Bisulfite-Seq)
| PRJNA292132 | ENA
Project description:Allergic Airway Disease is Dependent on Methylene-Tetrahydrofolate Reductase
| PRJNA292134 | ENA
Project description:RATIONALE: The development and progression of asthma are strongly influenced by environmental exposures. We have demonstrated that mice exposed to a diet enriched with methyl donors during vulnerable periods of fetal development can enhance the heritable risk of allergic airway disease through epigenetic changes. OBJECTIVES: Since there is conflicting evidence on the role of folate in modifying allergic airway disease risk, we hypothesized that blocking folate metabolism through the loss of methylene-tetrahydrofolate reductase (MTHFR) activity would reduce the allergic airway disease phenotype. METHODS: Using a house dust mite (HDM) induced model of allergic airway disease, we tested the effect of MTHFR on disease severity. MEASUREMENTS AND MAIN RESULTS: Loss of MTHFR alters single carbon metabolite levels in the lung and serum including elevated homocysteine and cystathionine and reduced methionine. HDM-treated C57BL/6MTHFR-/- mice demonstrate significantly less airway hyerreactivity (AHR) compared to HDM-treated C57BL/6 mice. Furthermore, HDM-treated C57BL/6MTHFR-/- mice compared to HDM-treated C57BL/6 mice have reduced whole lung lavage (WLL) cellularity, eosinophilia, and IL-4/IL-5 cytokine concentrations. The effect of MTHFR loss on HDM-induced allergic airway disease was reversed by betaine supplementation. 737 genes are differentially expressed and 146 regions are differentially methylated in lung tissue from HDM-treated C57BL/6MTHFR-/- mice and HDM-treated C57BL/6 mice. Additionally, analysis of methylation/expression relationships identified 503 significant correlations. CONCLUSION: Collectively, these findings indicate that single carbon metabolism warrants further investigation as a disease modifier in allergic airway disease.
2018-01-31 | GSE71822 | GEO
Project description:RATIONALE: The development and progression of asthma are strongly influenced by environmental exposures. We have demonstrated that mice exposed to a diet enriched with methyl donors during vulnerable periods of fetal development can enhance the heritable risk of allergic airway disease through epigenetic changes. OBJECTIVES: Since there is conflicting evidence on the role of folate in modifying allergic airway disease risk, we hypothesized that blocking folate metabolism through the loss of methylene-tetrahydrofolate reductase (MTHFR) activity would reduce the allergic airway disease phenotype. METHODS: Using a house dust mite (HDM) induced model of allergic airway disease, we tested the effect of MTHFR on disease severity. MEASUREMENTS AND MAIN RESULTS: Loss of MTHFR alters single carbon metabolite levels in the lung and serum including elevated homocysteine and cystathionine and reduced methionine. HDM-treated C57BL/6MTHFR-/- mice demonstrate significantly less airway hyerreactivity (AHR) compared to HDM-treated C57BL/6 mice. Furthermore, HDM-treated C57BL/6MTHFR-/- mice compared to HDM-treated C57BL/6 mice have reduced whole lung lavage (WLL) cellularity, eosinophilia, and IL-4/IL-5 cytokine concentrations. The effect of MTHFR loss on HDM-induced allergic airway disease was reversed by betaine supplementation. 737 genes are differentially expressed and 146 regions are differentially methylated in lung tissue from HDM-treated C57BL/6MTHFR-/- mice and HDM-treated C57BL/6 mice. Additionally, analysis of methylation/expression relationships identified 503 significant correlations. CONCLUSION: Collectively, these findings indicate that single carbon metabolism warrants further investigation as a disease modifier in allergic airway disease.
2018-01-31 | GSE71821 | GEO
Project description:Betaine critically contributes to the control of hepatocellular hydration and provides protection of the liver from different kinds of stress. This study investigates to what extent hepatocellular hydration changes affect the expression levels of enzymes involved in the metabolism of betaine and related organic osmolytes by using qRT-PCR gene expression studies in rat hepatoma cells as well as metabolic and gene expression profiling in 5,10 - methylene tetrahydrofolate reductase (MTHFR) deficient primary hepatocytes. The results demonstrate a coordinated regulation of betaine degradation and synthesis under anisoosmotic conditions. Expression of betaine degrading enzymes is downregulated by hyperosmolarity and strongly induced by hypoosmolarity. In contrast, synthesis of glycerophosphocholine from phosphoethanolamine and conversion of choline to betaine are both induced by hyperosmolarity but decreased under hypoosmotic conditions. In addition we evaluated the flux of choline and its derivates in liver and plasma of methylene tetrahydrofolate reductase knockout (Mthfr-/-) mice by tandem mass spectrometry. Analyses of system-wide alterations of osmolyte metabolism with microarray studies revealed expression changes similar to those after hypoosmotic exposure in this betaine depletion model. In conclusion, regulation of betaine synthesis and degradation and concomitant changes in intracellular osmolyte concentrations contribute to long-term adaptation to anisoosmotic exposure of the liver.
2013-04-01 | GSE42275 | GEO
Project description:Betaine critically contributes to the control of hepatocellular hydration and provides protection of the liver from different kinds of stress. This study investigates to what extent hepatocellular hydration changes affect the expression levels of enzymes involved in the metabolism of betaine and related organic osmolytes by using qRT-PCR gene expression studies in rat hepatoma cells as well as metabolic and gene expression profiling in 5,10 - methylene tetrahydrofolate reductase (MTHFR) deficient primary hepatocytes. The results demonstrate a coordinated regulation of betaine degradation and synthesis under anisoosmotic conditions. Expression of betaine degrading enzymes is downregulated by hyperosmolarity and strongly induced by hypoosmolarity. In contrast, synthesis of glycerophosphocholine from phosphoethanolamine and conversion of choline to betaine are both induced by hyperosmolarity but decreased under hypoosmotic conditions. In addition we evaluated the flux of choline and its derivates in liver and plasma of methylene tetrahydrofolate reductase knockout (Mthfr-/-) mice by tandem mass spectrometry. Analyses of system-wide alterations of osmolyte metabolism with microarray studies revealed expression changes similar to those after hypoosmotic exposure in this betaine depletion model. In conclusion, regulation of betaine synthesis and degradation and concomitant changes in intracellular osmolyte concentrations contribute to long-term adaptation to anisoosmotic exposure of the liver. Expression of 280 genes were analyzed in wild type and mthr-/- mice (n=7) with spotted oligonucleotides.
2013-04-01 | E-GEOD-42275 | biostudies-arrayexpress
Project description:Distinct roles of FOXA2 and FOXA3 in allergic airway disease
| PRJNA109809 | ENA
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
| S-EPMC8784167 | biostudies-literature
Project description:Obesity is associated with severe, difficult to control asthma, and increased airway oxidative stress. Mitochondrial reactive oxygen species (mROS) are an important source of oxidative stress leading us to hypothesize that targeting mROS in obese allergic asthma might be an effective treatment strategy. Using a mouse model of house dust mite (HDM) induced allergic airway disease in mice fed a low- (LFD) or high-fat diet (HFD), and the mitochondrial antioxidant MitoQuinone (MitoQ); we investigated the effects of obesity and mROS on airway inflammation, remodelling and airway hyperreactivity (AHR). HDM induces airway inflammation, remodelling and hyperreactivity in both lean and obese mice. Obese allergic mice showed increased lung tissue eotaxin levels, airway tissue eosinophilia and AHR when compared to lean allergic mice. MitoQ reduced markers of airway inflammation, remodelling and hyperreactivity in both lean and obese allergic mice, and tissue eosinophilia in obeseHDM mice. mROS regulates cell signalling by protein oxidation of multiple downstream targets: MitoQ reduced HDM-induced cysteine-sulfenylation of several proteins including those involved in the unfolded protein response (UPR). In summary, mROS mediates the development of allergic airway disease and hence MitoQ might be effective for the treatment for asthma, and specific features of obese asthma.
2023-06-02 | PXD029715 | Pride
Project description:To characterize the genetic basis of hybrid male sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven ‘hotspots,’ seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL - but not cis eQTL - were substantially lower when mapping was restricted to a ‘fertile’ subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility.
2014-05-01 | GSE54089 | GEO