Expression data (mRNA) from GD-9.5 (E9.5), Folr1+/+ (Folr1 WT) and Folr-/- (Folr1 KO) mouse embryos
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE155428 | GEO | 2021/02/10
REPOSITORIES: GEO
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Project description:Defective function of FolR1 in mice results in inadequate transport, accumulation, or metabolism of folate during cardiovascular morphogenesis. We have observed cardiovascular abnormalities including outflow track defects and aortic arch artery defects in these genetically compromised mice. In order to investigate the mechanisms underlying the failure to complete cardiac development in the transgenic mouse model, we studied gene expression difference between FolR1 knockout embryos and normal embryos during outflow track septation (GD11:12, GSM78976 ... GSM78987), and studied gene expression difference between FolR1 knockout embryos and normal embryos during embryonic heart development(GD9:00 and GD10:00, GSM79024 ... GSM79035). Keywords: gene ablation response
2006-02-20 | GSE3487 | GEO
Project description:The reduced folate carrier (RFC1) is an integral membrane protein and facilitative anion exchanger that mediates delivery of 5-methyltetrahydrofolate into mammalian cells. Adequate maternal-fetal transport of folate is necessary for normal embryogenesis. Targeted inactivation of the murine RFC1 gene results in post-implantation embryo lethality, but daily folic acid supplementation of pregnant dams prolongs survival of homozygous embryos until mid-gestation. At E10.5 RFC1-/- embryos are developmentally delayed relative to wildtype littermates, have multiple malformations, including neural tube defects, and die due to failure of chorioallantoic fusion. The mesoderm is sparse and disorganized, and there is a marked absence of erythrocytes in yolk sac blood islands. Affymetrix microarray analysis and quantitative RT-PCR validation of the relative gene expression profiles in E9.5 RFC1-/- vs. RFC1+/+ embryos indicates a dramatic downregulation of multiple genes involved in erythropoiesis, and upregulation of several genes that form the cubilin-megalin multiligand endocytic receptor complex. Megalin protein expression disappears from the visceral yolk sac of RFC1-/- embryos, and cubilin protein is widely misexpressed. Inactivation of RFC1 impacts the expression of several ligands and interacting proteins in the cubilin-amnionless-megalin complex that are involved in the maternal-fetal transport of folate, vitamin B12, and other nutrients, lipids and morphogens required for normal embryogenesis. Comparison of RFC KO, wildtype normal embryos vs. RFC KO, nullizygous affected embryos Experiment Overall Design: 6 samples RFC KO mouse embryos, E9.5, folic acid treated: 3 Control, Wildtype, normal; 3 Affected, Nullizygous, CR/chorioallantoic defect; as paired-littermates with one normal and one affected embryo per set from each of three separate litters for RNA extraction and hybridization on Affymetrix microarrays.
2008-04-05 | E-GEOD-10659 | biostudies-arrayexpress
Project description:The reduced folate carrier (RFC1) is an integral membrane protein and facilitative anion exchanger that mediates delivery of 5-methyltetrahydrofolate into mammalian cells. Adequate maternal-fetal transport of folate is necessary for normal embryogenesis. Targeted inactivation of the murine RFC1 gene results in post-implantation embryo lethality, but daily folic acid supplementation of pregnant dams prolongs survival of homozygous embryos until mid-gestation. At E10.5 RFC1-/- embryos are developmentally delayed relative to wildtype littermates, have multiple malformations, including neural tube defects, and die due to failure of chorioallantoic fusion. The mesoderm is sparse and disorganized, and there is a marked absence of erythrocytes in yolk sac blood islands. Affymetrix microarray analysis and quantitative RT-PCR validation of the relative gene expression profiles in E9.5 RFC1-/- vs. RFC1+/+ embryos indicates a dramatic downregulation of multiple genes involved in erythropoiesis, and upregulation of several genes that form the cubilin-megalin multiligand endocytic receptor complex. Megalin protein expression disappears from the visceral yolk sac of RFC1-/- embryos, and cubilin protein is widely misexpressed. Inactivation of RFC1 impacts the expression of several ligands and interacting proteins in the cubilin-amnionless-megalin complex that are involved in the maternal-fetal transport of folate, vitamin B12, and other nutrients, lipids and morphogens required for normal embryogenesis. Comparison of RFC KO, wildtype normal embryos vs. RFC KO, nullizygous affected embryos Keywords: reduced folate carrier knockout, folate receptor, cubilin, megalin, embryos, gene expression, neural tube defect, chorioallantoic fusion
2008-03-17 | GSE10659 | GEO
Project description:Defective function of FolR1 in mice results in inadequate transport, accumulation, or metabolism of folate during cardiovascular morphogenesis. We have observed cardiovascular abnormalities including outflow track defects and aortic arch artery defects in these genetically compromised mice. In order to investigate the mechanisms underlying the failure to complete cardiac development in the transgenic mouse model, we studied gene expression difference between FolR1 knockout embryos and normal embryos during outflow track septation (GD11:12, GSM78976 ... GSM78987), and studied gene expression difference between FolR1 knockout embryos and normal embryos during embryonic heart development(GD9:00 and GD10:00, GSM79024 ... GSM79035). Keywords: gene ablation response Pregnant FolR1 heterozygotic dams were supplemented with s-folinic acid 6.25mg/kg/day p.o. At GD11:12, 3 control embryos and 3 null embryos were harvested from 6 different dams. From these embryos, the conotruncus tissue of developing heart was dissected and RNA extracted. These RNA samples were used for hybridization on commercially available CodeLink UniSet 10K Bioarray. Pregnant FolR1 heterozygotic dams were supplemented with s-folinic acid 6.25mg/kg/day p.o. At GD9:00 and GD10:00, 3 control embryos and 3 null embryos were harvested from 6 different dams for each timepoint. From these embryos, the heart tissue of developing heart was dissected and RNA extracted. These RNA samples were used for hybridization on commercially available CodeLink UniSet 20K Bioarray.
2006-02-20 | E-GEOD-3487 | biostudies-arrayexpress
Project description:Defects in homocysteine and folate metabolism are associated with increased risks for neural tube and congenital heart defects, cardiovascular disease and stroke, cancers, and neurodegeneration. In many but not all cases, dietary supplementation with folate significantly reduces the severity and incidence of these conditions. Common polymorphisms modulate these metabolic pathways and disease risks, but do not fully account for the particular birth defects and adult diseases that occur in at-risk individuals. To test whether other pathways contribute to disease pathogenesis, we analyzed global and pathway-specific changes in gene expression and levels of selected metabolites after depletion and repletion of dietary folate in two genetically distinct inbred strains of mice. Compared to the C57BL/6J strain, A/J showed greater homeostatic response to folate perturbation by retaining a higher serum folate level and minimizing global gene expression changes. Remarkably, folate perturbation led to systematic strain-specific differences only in the expression profile of the cholesterol biosynthesis pathway and translated to changes in levels of serum and liver total cholesterol. By genetically increasing serum and liver total cholesterol levels in APOE deficient mice, we modestly but significantly improved folate retention during folate depletion, suggesting an interplay between homocysteine and folate metabolism and cholesterol metabolism. Absence of measurable changes in global methylation patterns or amelioration of effects with supplementation with an alternative methyl donor suggest that dietary folate perturbations do not act through large-scale or general changes in methylation. These results suggest that homeostatic responses in cholesterol metabolism contribute to the beneficial effects of dietary folate supplementation. Keywords: time course, stress response, diet, genetic, homeostasis Six-week old female A/J and C57BL/6J mice were purchased from the Jackson Laboratory. All mice were raised on a control diet containing four ppm folic acid (Basal Diet 5755, TestDiet) for one week before the start of studies. Selected mice were then placed on folic acid deficient diet (58C3, TestDiet) containing 1% succinylsulfathiazole, a non-absorbable antibiotic commonly used to suppress folate production by bacteria in the intestine. We had nine different treatment plans per strain with eight replicate mice per treatment. There were four folic acid depletion treatment in which mice were placed on folic acid deficient diet for 1, 2, 7, or 14 days. There were two folic acid repletion treatment in which mice were placed on folic acid deficient diet for 14 days followed by 1 day on control diet and another set of mice on 14 days of folic acid deficient diet followed by 7 days of control diet. There were three control time points in which mice were placed on the control diet for 0, 9, or 22 days. Eight biological replicate liver tissue from each treatment was pooled and total RNA from each pool and total RNA from Universal Mouse Reference RNA (Stratagene) were aminoallyl labeled with Cy3 and Cy5 in duplicate, with reversing of dyes.
2008-08-27 | E-GEOD-9242 | biostudies-arrayexpress
Project description:Expression data (mRNA) from GD-9.5 (E9.5), Folr1+/+ (Folr1 WT) and Folr-/- (Folr1 KO) mouse embryos
| PRJNA649739 | ENA
Project description:Defects in homocysteine and folate metabolism are associated with increased risks for neural tube and congenital heart defects, cardiovascular disease and stroke, cancers, and neurodegeneration. In many but not all cases, dietary supplementation with folate significantly reduces the severity and incidence of these conditions. Common polymorphisms modulate these metabolic pathways and disease risks, but do not fully account for the particular birth defects and adult diseases that occur in at-risk individuals. To test whether other pathways contribute to disease pathogenesis, we analyzed global and pathway-specific changes in gene expression and levels of selected metabolites after depletion and repletion of dietary folate in two genetically distinct inbred strains of mice. Compared to the C57BL/6J strain, A/J showed greater homeostatic response to folate perturbation by retaining a higher serum folate level and minimizing global gene expression changes. Remarkably, folate perturbation led to systematic strain-specific differences only in the expression profile of the cholesterol biosynthesis pathway and translated to changes in levels of serum and liver total cholesterol. By genetically increasing serum and liver total cholesterol levels in APOE deficient mice, we modestly but significantly improved folate retention during folate depletion, suggesting an interplay between homocysteine and folate metabolism and cholesterol metabolism. Absence of measurable changes in global methylation patterns or amelioration of effects with supplementation with an alternative methyl donor suggest that dietary folate perturbations do not act through large-scale or general changes in methylation. These results suggest that homeostatic responses in cholesterol metabolism contribute to the beneficial effects of dietary folate supplementation. Keywords: time course, stress response, diet, genetic, homeostasis Six-week old female C57BL/6J and B6.129P2-Apoetm1Unc/J (Piedrahita et al. 1992) mice were purchased from the Jackson Laboratory. All mice were raised on a control diet containing four ppm folic acid (Basal Diet 5755, TestDiet) for one week before the start of studies. Mice were then placed on folic acid deficient diet (58C3, TestDiet) containing 1% succinylsulfathiazole, a non-absorbable antibiotic commonly used to suppress folate production by bacteria in the intestine, for 14 days. A subset of these mice were placed back on control diet for 7 days after 14 day depletion. There were three groups of mice that underwent folic acid depletion and repletion. ApoE knockout mice on C57BL/6J background, C57BL/6J mice supplemented with 25mM choline and 50mM saccharine in drinking water, and C57BL/6J mice supplemented with 50mM saccharine. Saccharine was used to reduce the bitter taste of choline in the drinking water. We also had C57BL/6J mice on the control diet for 14 days and 21 days. These mice served as controls for treated mice from each time point during hybridization. The folate level in the control diet for this study was significantly lower than the previous study (GSE9242) due to greater loss of folic acid by irradiation of the diet. There were eight replicate mice per treatment group per folic acid perturbation protocol. An equal amount (by weight) of liver tissue from eight replicate mice was separated into two pools of four replicate tissues each. Pooled RNA from treated mice and pooled RNA from control mice for each time point were aminoallyl labeled with Cy3 and Cy5 in duplicate with reversing of dyes.
2008-08-27 | E-GEOD-9243 | biostudies-arrayexpress
Project description:Neural tube defects (NTDs) are serious birth defects with an estimated worldwide incidence of 1 per 1,000 live births. The multifactorial nature of NTDs in humans has made it difficult to elucidate pathogenesis mechanisms. However, a strong relationship has been established between folate-homocysteine metabolism and NTD risk. Prevention of a substantial proportion of fetal NTDs can be achieved through maternal folic acid (FA) supplementation. However the mechanism by which FA exerts its beneficial effect remains unclear. METHODS: To improve our understanding of the underlying mechanisms of NTD pathogenesis and the ways in which folate exerts its beneficial effect, we analyzed mRNA profiles as well as folate and vitamin B12 levels in five NTD mouse mutants whose response to dietary FA was previously established. RESULTS: Differentially expressed genes representing the effect of each NTD-causing mutation were identified and associated with biologic pathways. Interestingly, the panel of NTD mutants collectively revealed pathways related to two nuclear receptors, retinoid X receptor (RXR) and pregnane X receptor (PXR), suggesting that these pathways may be related to a shared mechanism of NTD development. Moreover, the NTD-causing mutations that were associated with FA responsiveness had expression profiles that were related to folate-homocysteine metabolic pathways. These pathways were not strongly associated with mutants that do not respond to FA supplementation, implying that FA may be beneficial when the NTD mutation affects pathways related to folate-homocysteine metabolism. 5 groups of NTD mutants were studied. From each mutant group Heterozygous (test) and wild-type (control) female pups were used for this study at 6-8 weeks of age. 4 biological replicates were used for each of the test and control groups of each mutant. All mice used for the experiments were fasted 4-5 hours before dissection. A total of 36 samples were analyzed.
2013-09-30 | E-GEOD-51285 | biostudies-arrayexpress
Project description:Genetic modifiers of Syndromic Orofacial Clefts
| PRJNA671480 | ENA
Project description:Genetic modifiers of Syndromic Orofacial Clefts
| PRJNA671479 | ENA