Sod2 KO anemic mice
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ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE27053 | GEO | 2011/02/04
SECONDARY ACCESSION(S): PRJNA137637
REPOSITORIES: GEO
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Project description:Gene expression profiling was performed using Anemic Sod 2 Knockout mice and was compared to Gene expression profiles from Sod 2 WT mice. Background: Our laboratory is interested in the role of oxidative stress in aging and human disease. Currently, a major focus of our efforts is the characterization of a murine hemolytic anemia resulting from oxidative stress, a model for the human disorder Sideroblastic Anemia. This model is based upon transplantation of hematopoietic stem cells from mice that are deficient in the antioxidant protein SOD2 (Friedman J. Exp. Med. 2001 193:925). SOD2 protects against the cytotoxicity of mitochondrial superoxide produced as a byproduct of oxidative phosphorylation (Weisiger J. Biol. Chem. 1973 248:4793). In characterization of the model to date, we have focused upon RBC proteomic analysis to identify 41 proteins differentially expressed when comparing membrane and soluble RBC fractions from SOD2-/- vs. SOD2+/+ mice (Friedman et al. submitted). In addition, we have characterized the in vivo response of animals to a novel catalytic antioxidant (Euk-189) that has b! oth SOD and catalase activities. In addition to proteins involved in mitochondrial function and stress response we find a number of cell surface molecules with significant differential expression. Thrombospondin is found at higher levels in SOD2-/- red cell membrane fractions. This is an extracellular matrix glycoprotein involved in cell adhesion and migration that interacts with glycosaminoglycans (especially the heparan sulfate proteoglycan perlecan) expressed at the endothelial cell surface (Feitsma J. Biol. Chem. 2000 275:9396, Vischer Eur. J. Cell. Biol. 1997 73:332, Sun J. Biol. Chem. 1989 15:2885). Thrombospondin is likely an acquired surface molecule on our red cells, which is of interest as this molecule has been found on the surface of sickle red cells and appears to mediate abnormal adhesion of red cells to vessel wall (Hillery Blood 1996 87:4879, Sugihara Blood 1992 15:2634). CD44 is also found at higher levels in SOD2-/- membrane fractions. CD44 is an adhesion receptor for the high molecular weight polysaccharide hyaluronic acid and has been shown recently to be involved in the trafficking of stem cells to the bone marrow (Avigdor Blood January 2004). Higher expression of these molecules on the surface of SOD2-/- red cells may affect their adhesive interactions with vascular endothelium and may in part explain the early removal of these cells from the circulationóresulting in the observed hemolytic anemia. Some proteins that accumulate on the surface of SOD2 deficient red cells are likely molecular damage sensors, binding to surfaces altered by oxidative damage. The role of specific glycoproteins in such binding remains to be elucidated. Additional surface proteins from red cells show differential expression, many of which are also glycosylated. Planned Experiment: As the next step in characterization of the anemia model, we will compare the gene expression profile of red cell progenitors isolated from Sod2-/- and Sod2+/+ animals. We have defined cell-sorting conditions for isolation of erythroid progenitor cells from marrow of our mice.
2011-02-04 | E-GEOD-27053 | biostudies-arrayexpress
Project description:Superoxide dismutases (SOD) convert superoxide to hydrogen peroxide and therefore provide an important ROS defence mechanism. SOD2 is the sole superoxide dismutase in mitochondrial matrix and thus SOD2 knockout mice can be utilized to analyse what effects increased oxidative stress has on mitochondrial proteome. To this end, we purified heart mitochondria from heart Sod2 knockout mice (Sod2 Ckmm cre) and controls and analysed their proteome with label free LS MS/MS.
2018-06-06 | PXD008998 | Pride
Project description:The mitochondrial superoxide dismutase (SOD2) is a major antioxidant protein which detoxifies superoxide anion radicals generated by mitochondrial respiration (Weisiger and Fridovich, J. Biol. Chem. 1973). We designed a model of oxidative stress-induced anemia caused by SOD2-deficiency (Friedman et al. J. Exp. Med. 2001). Our previous work showed that mice reconstituted with SOD2-deficient hematopoietic stem cells develop an anemia with striking similarity to human sideroblastic anemia (SA) (Friedman et al. Blood 2004; Martin et al. Exp Hematol 2005). Our overall goal was to define early events in the pathogenesis of SOD2-deficiency SA and, in particular, to identify genes involved in the response of erythroid progenitors to oxidative stress. We compared gene expression of sorted TER-119+ CD71+ erythroblasts from SOD2-/- ('KO') versus Sod2+/+ ('WT') hematopoietic stem cell recipients using cDNA microarrays. Samples used in this study were re-hybridized with GLYCOv2 oligonucleotide arrays. GLYCOv2 oligonucleotide arrays are custom Affymetrix GeneChip arrays (Affymetrix, Santa Clara, CA) designed for the Functional Glycomics Gateway, collaboration between the Consortium for Functional Glycomics (CFG, http://www.functionalglycomics.org/) and Nature Publishing Group. A complete description of the array can be found at http://www.functionalglycomics.org/static/consortium/resources/resourcecoree.shtml . Hybridization results and quality control details can be found at https://www.functionalglycomics.org/glycomics/publicdata/microarray.jsp , by clicking on the ‘Raw Data’ icon link for microarray experiment ‘Jeff Friedman 1: Sod2 KO anemic mice’. Briefly but importantly, one Sod2-/- sample, which was prepared separately, and whose GAPDH 3'/5' ratio was off range, was legitimately removed from the analysis of the GLYCOv2 and 430 2.0 arrays. Keywords: Genotype comparison, genetic modification
2008-08-06 | GSE8726 | GEO
Project description:The mitochondrial superoxide dismutase (SOD2) is a major antioxidant protein which detoxifies superoxide anion radicals generated by mitochondrial respiration (Weisiger and Fridovich, J. Biol. Chem. 1973). We designed a model of oxidative stress-induced anemia caused by SOD2-deficiency (Friedman et al. J. Exp. Med. 2001). Our previous work showed that mice reconstituted with SOD2-deficient hematopoietic stem cells develop an anemia with striking similarity to human sideroblastic anemia (SA) (Friedman et al. Blood 2004; Martin et al. Exp Hematol 2005). Our overall goal was to define early events in the pathogenesis of SOD2-deficiency SA and, in particular, to identify genes involved in the response of erythroid progenitors to oxidative stress. We compared gene expression of sorted TER-119+ CD71+ erythroblasts from SOD2-/- ('KO') versus Sod2+/+ ('WT') hematopoietic stem cell recipients using cDNA microarrays. Samples used in this study were re-hybridized with GLYCOv2 oligonucleotide arrays. GLYCOv2 oligonucleotide arrays are custom Affymetrix GeneChip arrays (Affymetrix, Santa Clara, CA) designed for the Functional Glycomics Gateway, collaboration between the Consortium for Functional Glycomics (CFG, http://www.functionalglycomics.org/) and Nature Publishing Group. A complete description of the array can be found at http://www.functionalglycomics.org/static/consortium/resources/resourcecoree.shtml . Hybridization results and quality control details can be found at https://www.functionalglycomics.org/glycomics/publicdata/microarray.jsp , by clicking on the âRaw Dataâ icon link for microarray experiment âJeff Friedman 1: Sod2 KO anemic miceâ. Briefly but importantly, one Sod2-/- sample, which was prepared separately, and whose GAPDH 3'/5' ratio was off range, was legitimately removed from the analysis of the GLYCOv2 and 430 2.0 arrays. Experiment Overall Design: We sorted Sod2-/- and Sod2+/+ size-matched mouse erythroblasts based on the expression of two developmental surface markers, CD71 and TER-119. Total RNA from 4 biological replicates per genotype were extracted and hybridized on 8 Affymetrix Mouse Genome 430 2.0 arrays (Affymetrix, Santa Clara, CA). After quality controls (see scan protocol), analysis was performed with GeneSifter (VizX Labs, Seattle, WA) using 4 Sod2+/+ (control samples, WT) and 3 Sod2-/- (KO) replicates.
2008-10-25 | E-GEOD-8726 | biostudies-arrayexpress
Project description:The purinergic receptor P2Y13 (P2RY13) has been shown to play a role in the uptake of holo-HDL particles in in vitro hepatocyte experiments. In order to determine the role of P2Y13 in lipoprotein metabolism in vivo, we ablated the expression of this gene in mice and found that P2Y13 knockout mice have lower plasma HDL (17%) and LDL (27%) levels as well as lower fecal concentrations of neutral sterols. In addition, significant decreases were detected in serum levels of fatty acids, glycerol and triglycerides in P2Y13 knockout mice. mRNA profiling analyses showed that ablation of P2Y13 affects hepatic gene expression in a gender-specific manner. Non-supervised agglomerative cluster analysis showed that expression changes in mice with the same genotype (KO or WT) cluster together and that distinct gene expression clusters can be observed for males and females. Subsequent gene set enrichment analysis showed increased expression of cholesterol and fatty acid biosynthesis genes, while fatty acid beta-oxidation genes were significantly decreased. Liver gene signatures also identified changes in SREBP-regulated and PPARgamma-regulated transcript levels. Differential gene expression upon P2RY13 gene ablation. Livers were isolated from male and female wildtype and P2RY13 knockout mice (6 per gender/genotype group, except for 5 per male/WT group). Isolated RNA was subjected to microarray analyses. The results of a one-way ANOVA analysis (p<0.05) showed 3471 transcripts whose relative expression changes were more than 20%.
2010-09-10 | E-GEOD-20920 | biostudies-arrayexpress
Project description:Analysis of gene expression in spleens of WT and Snd1 knockout (KO) mice
2020-01-25 | GSE144217 | GEO
Project description:Analysis of gene expression in livers of WT and Snd1 knockout (KO) mice.
2020-01-23 | GSE144060 | GEO
Project description:To compare the splenic macrophages between SIRPα-knockout mice and WT mice, we performed a complete transcript profiling of the splenic red pulp macrophages from SIRPα-KO mice compared to WT mice using mRNA microarray as a discovery platform. SIRPα-KO mice and WT mice were kept under the same condition. Macrophages were isolated from spleen red pulp of SIRPα-KO mice and WT mice. RNA was then isolated from the same number of freshly isolated macrophages.
2016-11-22 | GSE78191 | GEO
Project description:Proteomics analysis targeting cerebral cortex, hippocampus and cerebellum derived from AlkB homologues 8 (ALKBH8) knockout mice was conducted to identify differentially expressed proteins. Peptides were analyzed by DIA proteome analysis method using Orbitrap Eclipse, and proteins with variable expression were comprehensively analyzed by library-free method using DIA-NN.
2024-10-18 | PXD046196 | JPOST Repository
Project description:The purinergic receptor P2Y13 (P2RY13) has been shown to play a role in the uptake of holo-HDL particles in in vitro hepatocyte experiments. In order to determine the role of P2Y13 in lipoprotein metabolism in vivo, we ablated the expression of this gene in mice and found that P2Y13 knockout mice have lower plasma HDL (17%) and LDL (27%) levels as well as lower fecal concentrations of neutral sterols. In addition, significant decreases were detected in serum levels of fatty acids, glycerol and triglycerides in P2Y13 knockout mice. mRNA profiling analyses showed that ablation of P2Y13 affects hepatic gene expression in a gender-specific manner. Non-supervised agglomerative cluster analysis showed that expression changes in mice with the same genotype (KO or WT) cluster together and that distinct gene expression clusters can be observed for males and females. Subsequent gene set enrichment analysis showed increased expression of cholesterol and fatty acid biosynthesis genes, while fatty acid beta-oxidation genes were significantly decreased. Liver gene signatures also identified changes in SREBP-regulated and PPARgamma-regulated transcript levels.
2010-09-10 | GSE20920 | GEO