Transcription profiling of limb buds from E12.5 wild type and POR conditional knock out mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Katy Schmidt
PROVIDER: E-TABM-367 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Cytochrome P450 oxidoreductase (POR) is involved in the oxidative metabolism of xenobiotics and endogenous compounds like fatty acid and cholesterol. While effects of diminished Por were extensively studied in mouse models, studies in human models are still missing. We used previously established CRISPR/Cas9-mediated POR knockdown in HepaRG cells as a human hepatic cell model to investigate the effects of POR knockdown on global protein expression levels.
2021-11-04 | PXD028577 | Pride
Project description:The cytochrome P450 reductase (POR) transfers electrons to all microsomal cytochrome P450 enzymes (CYP450) thereby driving their activity. In the vascular system, the POR/CYP450 system has been linked to the production of epoxyeicosatrienoic acids (EETs) but also to the generation of reactive oxygen species. In cardiac myocytes (CMs), EETs have been shown to modulate the cardiac function and have cardioprotective effects. The functional importance of the endothelial POR/CYP450 system in the heart is unclear and was studied here using endothelial cell-specific, inducible knockout mice of POR (ecPOR-/-). RNA sequencing of murine cardiac cells revealed a cell type-specific expression of different CYP450 homologues. Cardiac endothelial cells mainly expressed members of the CYP2 family which produces EETs, and of the CYP4 family that generates omega fatty acids. Tamoxifen-induced endothelial deletion of POR in mice led to cardiac remodelling under basal conditions, as shown by an increase in heart weight to body weight ratio and an increased CM area as compared to control animals. Endothelial deletion of POR was associated with a significant increase in endothelial genes linked to protein synthesis with no changes in genes of the oxidative stress response. CM of ecPOR-/- mice exhibited attenuated expression of genes linked to mitochondrial function and an increase in genes related to cardiac myocyte contractility. In a model of pressure overload (transverse aortic constriction, TAC with O-rings), ecPOR-/- mice exhibited an accelerated reduction in cardiac output (CO) and stroke volume (SV) as compared to control mice. These results suggest that loss of endothelial POR along with a reduction in EETs leads to an increase in vascular stiffness and loss in cardioprotection, resulting in cardiac remodelling.
2022-12-21 | GSE214776 | GEO
Project description:Transcription profiling by array of limb buds from E12.5 POR knock-out mice
2015-11-02 | E-TABM-367 | ExpressionAtlas
Project description:Using mice deficient in hepatic cytochrome-P450 oxidoreductase (POR), which disables the liver cytochrome P450 system, the metabolism and biological response of the anti-carcinogenic flavonoid, quercetin, was examined. Profiling circulating metabolites revealed similar profiles over 72 h in wild type (WT) and POR-null (KO) mice, showing that hepatic P450 and reduced biliary secretion do not affect quercetin metabolism. Transcriptional profiling at 24 h revealed that 2-3 fold more genes responded significantly to quercetin in WT compared to KO in the jejunum, ileum, colon, and liver, suggesting that hepatic P450s mediate many of the biological effects of quercetin, such as immune function, estrogen receptor signaling and lipid, glutathione, purine, and amino acid metabolism, even though quercetin metabolism is not modified. The functional interpretation of expression data in response to quercetin (single dose of 7 mg/animal) revealed a molecular relationship between the liver and jejunum. In WT animals, amino acid and sterol metabolism were predominantly modulated in the liver, fatty acid metabolism response was shared between the liver and jejunum, and glutathione metabolism was modulated in the small intestine. In contrast, KO animals do not regulate amino acid metabolism in the liver or small intestine, they share the control of fatty acid metabolism between the liver and jejunum, and regulation of sterol metabolism is shifted from the liver to the jejunum and that of glutathione metabolism from the jejunum to the liver. This demonstrates that the quercetin-mediated regulation of these biological functions in extrahepatic tissues is dependent on the functionality of the liver POR. In conclusion, using a systems biology approach to explore the contribution of hepatic phase I detoxification on quercetin metabolism demonstrated the resiliency and adaptive capacity of a biological organism in dealing with a bioactive nutrient when faced with a tissue-specific molecular dysfunction. Keywords: nutritional intervention, comparative genomic response, genotype variation
2006-03-01 | GSE4256 | GEO
Project description:Using mice deficient in hepatic cytochrome-P450 oxidoreductase (POR), which disables the liver cytochrome P450 system, the metabolism and biological response of the anti-carcinogenic flavonoid, quercetin, was examined. Profiling circulating metabolites revealed similar profiles over 72 h in wild type (WT) and POR-null (KO) mice, showing that hepatic P450 and reduced biliary secretion do not affect quercetin metabolism. Transcriptional profiling at 24 h revealed that 2-3 fold more genes responded significantly to quercetin in WT compared to KO in the jejunum, ileum, colon, and liver, suggesting that hepatic P450s mediate many of the biological effects of quercetin, such as immune function, estrogen receptor signaling and lipid, glutathione, purine, and amino acid metabolism, even though quercetin metabolism is not modified. The functional interpretation of expression data in response to quercetin (single dose of 7 mg/animal) revealed a molecular relationship between the liver and jejunum. In WT animals, amino acid and sterol metabolism were predominantly modulated in the liver, fatty acid metabolism response was shared between the liver and jejunum, and glutathione metabolism was modulated in the small intestine. In contrast, KO animals do not regulate amino acid metabolism in the liver or small intestine, they share the control of fatty acid metabolism between the liver and jejunum, and regulation of sterol metabolism is shifted from the liver to the jejunum and that of glutathione metabolism from the jejunum to the liver. This demonstrates that the quercetin-mediated regulation of these biological functions in extrahepatic tissues is dependent on the functionality of the liver POR. In conclusion, using a systems biology approach to explore the contribution of hepatic phase I detoxification on quercetin metabolism demonstrated the resiliency and adaptive capacity of a biological organism in dealing with a bioactive nutrient when faced with a tissue-specific molecular dysfunction. Keywords: nutritional intervention, comparative genomic response, genotype variation
2006-03-01 | GSE4259 | GEO
Project description:Using mice deficient in hepatic cytochrome-P450 oxidoreductase (POR), which disables the liver cytochrome P450 system, the metabolism and biological response of the anti-carcinogenic flavonoid, quercetin, was examined. Profiling circulating metabolites revealed similar profiles over 72 h in wild type (WT) and POR-null (KO) mice, showing that hepatic P450 and reduced biliary secretion do not affect quercetin metabolism. Transcriptional profiling at 24 h revealed that 2-3 fold more genes responded significantly to quercetin in WT compared to KO in the jejunum, ileum, colon, and liver, suggesting that hepatic P450s mediate many of the biological effects of quercetin, such as immune function, estrogen receptor signaling and lipid, glutathione, purine, and amino acid metabolism, even though quercetin metabolism is not modified. The functional interpretation of expression data in response to quercetin (single dose of 7 mg/animal) revealed a molecular relationship between the liver and jejunum. In WT animals, amino acid and sterol metabolism were predominantly modulated in the liver, fatty acid metabolism response was shared between the liver and jejunum, and glutathione metabolism was modulated in the small intestine. In contrast, KO animals do not regulate amino acid metabolism in the liver or small intestine, they share the control of fatty acid metabolism between the liver and jejunum, and regulation of sterol metabolism is shifted from the liver to the jejunum and that of glutathione metabolism from the jejunum to the liver. This demonstrates that the quercetin-mediated regulation of these biological functions in extrahepatic tissues is dependent on the functionality of the liver POR. In conclusion, using a systems biology approach to explore the contribution of hepatic phase I detoxification on quercetin metabolism demonstrated the resiliency and adaptive capacity of a biological organism in dealing with a bioactive nutrient when faced with a tissue-specific molecular dysfunction. Keywords: nutritional intervention, comparative genomic response, genotype variation
2006-03-01 | GSE4258 | GEO
Project description:Using mice deficient in hepatic cytochrome-P450 oxidoreductase (POR), which disables the liver cytochrome P450 system, the metabolism and biological response of the anti-carcinogenic flavonoid, quercetin, was examined. Profiling circulating metabolites revealed similar profiles over 72 h in wild type (WT) and POR-null (KO) mice, showing that hepatic P450 and reduced biliary secretion do not affect quercetin metabolism. Transcriptional profiling at 24 h revealed that 2-3 fold more genes responded significantly to quercetin in WT compared to KO in the jejunum, ileum, colon, and liver, suggesting that hepatic P450s mediate many of the biological effects of quercetin, such as immune function, estrogen receptor signaling and lipid, glutathione, purine, and amino acid metabolism, even though quercetin metabolism is not modified. The functional interpretation of expression data in response to quercetin (single dose of 7 mg/animal) revealed a molecular relationship between the liver and jejunum. In WT animals, amino acid and sterol metabolism were predominantly modulated in the liver, fatty acid metabolism response was shared between the liver and jejunum, and glutathione metabolism was modulated in the small intestine. In contrast, KO animals do not regulate amino acid metabolism in the liver or small intestine, they share the control of fatty acid metabolism between the liver and jejunum, and regulation of sterol metabolism is shifted from the liver to the jejunum and that of glutathione metabolism from the jejunum to the liver. This demonstrates that the quercetin-mediated regulation of these biological functions in extrahepatic tissues is dependent on the functionality of the liver POR. In conclusion, using a systems biology approach to explore the contribution of hepatic phase I detoxification on quercetin metabolism demonstrated the resiliency and adaptive capacity of a biological organism in dealing with a bioactive nutrient when faced with a tissue-specific molecular dysfunction. Keywords: nutritional intervention, comparative genomic response, genotype variation
2006-03-01 | GSE4257 | GEO
Project description:During limb development, Hoxd genes are transcribed in two waves: Early on, when the arm and forearm are specified and subsequently, when digits form. While the latter phase is controlled by enhancers centromeric to the HoxD cluster, we show here that the early phase requires enhancers located in the opposite telomeric gene desert. The transition between the two types of regulations involves a functional switch between two distinct topological domains, as reflected by a subset of genes mapping centrally into the cluster, which initially interact with the telomeric domain and subsequently shift to establish new contacts on the opposite side. This transition between two regulatory landscapes generates an intermediate area of low Hox dose developing into the wrist, the transition between our arms and our hands. This intriguing correspondence between genomic and morphological boundaries illustrates the mechanism underlying collinear Hox gene regulation in our developing appendages. Chromatin ImmoPrecipitation on chip (Tiling array): Distribution of H3K4me3 and H3K27me3 in early limb buds at E9.5, E10.5 and proximal late limbs E12.5. Distribution of H3K27me3 in del(8-13) and del(8-13)/del(attP-TpSB3) E10.5 limb buds. Distribution of H3K27me3 in WT and homozygote del(Nsi-Atf2) (Montavon et al., 2011) forelimb autopods.
2013-06-07 | E-GEOD-45454 | biostudies-arrayexpress
Project description:Using mice deficient in hepatic cytochrome-P450 oxidoreductase (POR), which disables the liver cytochrome P450 system, the metabolism and biological response of the anti-carcinogenic flavonoid, quercetin, was examined. Profiling circulating metabolites revealed similar profiles over 72 h in wild type (WT) and POR-null (KO) mice, showing that hepatic P450 and reduced biliary secretion do not affect quercetin metabolism. Transcriptional profiling at 24 h revealed that 2-3 fold more genes responded significantly to quercetin in WT compared to KO in the jejunum, ileum, colon, and liver, suggesting that hepatic P450s mediate many of the biological effects of quercetin, such as immune function, estrogen receptor signaling and lipid, glutathione, purine, and amino acid metabolism, even though quercetin metabolism is not modified. The functional interpretation of expression data in response to quercetin (single dose of 7 mg/animal) revealed a molecular relationship between the liver and jejunum. In WT animals, amino acid and sterol metabolism were predominantly modulated in the liver, fatty acid metabolism response was shared between the liver and jejunum, and glutathione metabolism was modulated in the small intestine. In contrast, KO animals do not regulate amino acid metabolism in the liver or small intestine, they share the control of fatty acid metabolism between the liver and jejunum, and regulation of sterol metabolism is shifted from the liver to the jejunum and that of glutathione metabolism from the jejunum to the liver. This demonstrates that the quercetin-mediated regulation of these biological functions in extrahepatic tissues is dependent on the functionality of the liver POR. In conclusion, using a systems biology approach to explore the contribution of hepatic phase I detoxification on quercetin metabolism demonstrated the resiliency and adaptive capacity of a biological organism in dealing with a bioactive nutrient when faced with a tissue-specific molecular dysfunction. Experiment Overall Design: All animals were adapted to the RM3 (E) 801710 Soya-free powdered diet (B. S & S. [Scotland] Ltd, UK) over a period of 14 days. Quercetin was added separately to the semi-purified diets at a concentration of 6200 ppm (0.62 %; 6.2 g per kg). 65 male cytochrome P450 reductase null (KO) mice and 65 wild type (WT) C57BL/6 mice were reared, all aged between 6-8 weeks. Animals were housed 3 per cage, where both temperature and relative humidity were maintained within a range of 19-23oC and 40-70%, respectively. Twelve-hour periods of light were cycled with twelve-hour periods of darkness. Experiment Overall Design: For each strain of mouse, the following experimental design was used: a control group (25 mice) receiving powdered RM3 diet ad libitum and a group (25 mice) receiving a âhigh doseâ of quercetin (7 mg / mouse). The experimental diet was administered on day 15, following a 14-day adaptation period to the RM3 diet. Animals were sacrificed after 24 h. Experiment Overall Design: RNA samples destined for microarray analysis were only accepted and pooled into three groups if no aberrant signs of degradation (e.g. multiple peaks) were observed. The comprehensive gene expression profiles of the liver, jejunum, ileum, and colon were analyzed. In all cases, except those listed, RNA from 3 mice was pooled to form sample 1, another 3 mice to form sample 2, etc. Thus, 9 mice were used for the four experimental groups: wild-type, wild-type+quercetin, POR-null, POR-null+quercetin.
2008-06-13 | E-GEOD-4258 | biostudies-arrayexpress
Project description:Using mice deficient in hepatic cytochrome-P450 oxidoreductase (POR), which disables the liver cytochrome P450 system, the metabolism and biological response of the anti-carcinogenic flavonoid, quercetin, was examined. Profiling circulating metabolites revealed similar profiles over 72 h in wild type (WT) and POR-null (KO) mice, showing that hepatic P450 and reduced biliary secretion do not affect quercetin metabolism. Transcriptional profiling at 24 h revealed that 2-3 fold more genes responded significantly to quercetin in WT compared to KO in the jejunum, ileum, colon, and liver, suggesting that hepatic P450s mediate many of the biological effects of quercetin, such as immune function, estrogen receptor signaling and lipid, glutathione, purine, and amino acid metabolism, even though quercetin metabolism is not modified. The functional interpretation of expression data in response to quercetin (single dose of 7 mg/animal) revealed a molecular relationship between the liver and jejunum. In WT animals, amino acid and sterol metabolism were predominantly modulated in the liver, fatty acid metabolism response was shared between the liver and jejunum, and glutathione metabolism was modulated in the small intestine. In contrast, KO animals do not regulate amino acid metabolism in the liver or small intestine, they share the control of fatty acid metabolism between the liver and jejunum, and regulation of sterol metabolism is shifted from the liver to the jejunum and that of glutathione metabolism from the jejunum to the liver. This demonstrates that the quercetin-mediated regulation of these biological functions in extrahepatic tissues is dependent on the functionality of the liver POR. In conclusion, using a systems biology approach to explore the contribution of hepatic phase I detoxification on quercetin metabolism demonstrated the resiliency and adaptive capacity of a biological organism in dealing with a bioactive nutrient when faced with a tissue-specific molecular dysfunction. Experiment Overall Design: All animals were adapted to the RM3 (E) 801710 Soya-free powdered diet (B. S & S. [Scotland] Ltd, UK) over a period of 14 days. Quercetin was added separately to the semi-purified diets at a concentration of 6200 ppm (0.62 %; 6.2 g per kg). 65 male cytochrome P450 reductase null (KO) mice and 65 wild type (WT) C57BL/6 mice were reared, all aged between 6-8 weeks. Animals were housed 3 per cage, where both temperature and relative humidity were maintained within a range of 19-23oC and 40-70%, respectively. Twelve-hour periods of light were cycled with twelve-hour periods of darkness. Experiment Overall Design: For each strain of mouse, the following experimental design was used: a control group (25 mice) receiving powdered RM3 diet ad libitum and a group (25 mice) receiving a âhigh doseâ of quercetin (7 mg / mouse). The experimental diet was administered on day 15, following a 14-day adaptation period to the RM3 diet. Animals were sacrificed after 24 h. Experiment Overall Design: RNA samples destined for microarray analysis were only accepted and pooled into three groups if no aberrant signs of degradation (e.g. multiple peaks) were observed. The comprehensive gene expression profiles of the liver, jejunum, ileum, and colon were analyzed. In all cases, except those listed, RNA from 3 mice was pooled to form sample 1, another 3 mice to form sample 2, etc. Thus, 9 mice were used for the four experimental groups: wild-type, wild-type+quercetin, POR-null, POR-null+quercetin.
2008-06-13 | E-GEOD-4256 | biostudies-arrayexpress