Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Differential gene expression in APOE3 and APOE4 gene targeted replacement mice

ABSTRACT: The aim of the study was to investigate hepatic gene expression profiles differentially regulated by the APOE genotype in gene targeted replacement mice. The APOE4 genotype is associated with increased mortality in the elderly and is an independent risk factor for age-dependent chronic diseases. However, little is known about the underlying mechanisms and molecular targets involved in the APOE4-risk association. As APOE is centrally involved in lipid and cholesterol metabolism and in large part is produced in the liver, we analyzed hepatic RNA profiles of APOE4- and APOE3-expressing mice. 2 groups of 5 animals with 1 liver extract per animal. Mice were homozygous for a human APOE3 or APOE4 gene targeted replacement of the endogenous mouse Apoe gene (B6.129P2-Apoetm2(APOE*3)Mae N8 or B6.129P2-Apoetm3(APOE*4)Mae N8, Taconic Transgenic ModelsM-bM-^DM-", http://www.taconic.com/wmspage.cfm?parm1=2542), purchased at the age of 6-8 weeks, strain C57BL/6, 3 months old at the performance of the microarray, 6 weeks on a high-fat diet containing 41% energy from milk fat and 2 g/kg cholesterol.

ORGANISM(S): Mus musculus

SUBMITTER: Gregor Warsow

PROVIDER: E-GEOD-42930 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Domino-like Effect of C112R Mutation on APOE4 Aggregation and Its Suppression by Alzheimer’s Disease Drug Candidate

Project description:The development of treatment for Alzheimer’s Disease (AD) is hindered by a limited understanding of its structural basis. Apolipoprotein E (APOE) ε4 genotype is the most important risk factor for late-onset AD. APOE4 differs from the APOE3 isoform by a single mutation, C112R. Here, we employ crystallography, biophysical methods and computer simulations to dissect the “domino-like” effect of C112R substitution on APOE4 behaviour. We found that the mutation induces long-distance (>15 Å) conformational changes leading to geometrically distinct T-shaped dimeric unit of APOE4 compared to APOE3. By mutagenesis, we demonstrate that the APOE4 unit is more prone to aggregation than that of the APOE3. AD drug candidate tramiprosate and metabolite 3-sulfopropanoic acid induce APOE3-like conformational behaviour in APOE4 and suppress its aggregation propensity. Omics analysis of APOE ε4/ε4 cerebral organoids treated with tramiprosate revealed its effect on cholesteryl esters, the storage product of excess cholesterol. Our results connect the APOE4 structure with its aggregation propensity, which can be further exploited in drug development for neurodegeneration and ageing.

2023-07-20 | PXD036416 | Pride

Gene co-expression networks identify Trem2 and Tyrobp as major hubs in human APOE expressing mice following traumatic brain injury.

Project description:To determine if there is an APOE isoform-specific response to TBI we performed controlled cortical impact on 3-month-old mice expressing human APOE3 or APOE4 isoforms. Following injury, we used several behavior paradigms to test for anxiety and learning and found that APOE3 and APOE4 targeted replacement mice demonstrate cognitive impairments following moderate TBI. Transcriptional profiling 14 days following injury revealed a significant effect of TBI, which was similar in both genotypes.

2017-07-29 | GSE102014 | GEO

Transcription profiling of mouse aorta genes of APOE-deficient animals receiving the ACE inhibitor captopril

Project description:Microarray gene expression profiling of aorta genes of APOE-deficient mice receiving atherosclerosis treatment with the ACE inhibitor captopril. Hypercholesterolemic APOE-deficient mice were used as a standard model of atherosclerosis to study gene expression changes during atherosclerosis treatment with the ACE inhibitor captopril. Microarray analysis was performed of whole aortas isolated from captopril-treated APOE-deficient mice relative to untreated APOE-deficient mice with overt atherosclerosis, and nontransgenic control mice. Microarray gene expression profiling revealed that captopril-mediated atherosclerosis prevention involved inhibition of aorta-infiltrating immune cells such as pro-atherogenic T lymphocytes and macrophages. Experiment Overall Design: Microarray gene expression profiling was performed of whole aortas isolated from APOE-deficient mice with atherosclerosis relative to captopril-treated APOE-deficient mice, and nontransgenic control mice. Three study groups were analyzed, i.e. 8-months-old untreated APOE-deficient mice with overt atherosclerosis, age-matched APOE-deficient mice treated for 7 months with the angiotensin-converting enzyme (ACE) inhibitor, captopril (20 mg/kg in drinking water), and nontransgenic control C57BL/6J mice. Two biological replicates were made of each group, and total RNA of three aortas was pooled for one gene chip.

2009-12-14 | E-GEOD-19286 | biostudies-arrayexpress

Microarray gene expression profiling of aortic genes of APOE-deficient mice receiving atherosclerosis treatment with the antioxidant vitamin E

Project description:Hypercholesterolemic APOE-deficient mice are a widely used experimental model of atherosclerosis and increased generation of reactive oxygen species (ROS) is a prominent feature of atherosclerosis development. To study the impact of ROS on atherogenesis, we treated APOE-deficient mice for 7 months with the antioxidant vitamin E (2000 IU/kg diet) and performed whole genome microarray gene expression profiling of aortic genes. Microarray gene expression profiling was performed of whole aortas isolated from vitamin E-treated APOE-deficient relative to untreated APOE-deficient mice with overt atherosclerosis, and nontransgenic B6 control mice. Microarray gene expression profiling revealed that vitamin E treatment prevented atherosclerosis-related gene expression changes of the aortic intima and media. Microarray gene expression profiling was performed of whole aortas isolated from APOE-deficient mice with atherosclerosis relative to vitamin E-treated APOE-deficient mice, and nontransgenic B6 control mice. Three study groups were analyzed, i.e. 8 months-old untreated APOE-deficient mice with overt atherosclerosis, age-matched APOE-deficient mice treated for 7 months with the antioxidant vitamin E (2000 IU/kd diet), and nontransgenic B6 control (C57BL/6J) mice. Two biological replicates were made of each group, and total RNA of three aortas was pooled for one gene chip. The study complements microarray study GSE19286.

2012-12-11 | E-GEOD-42813 | biostudies-arrayexpress

Effect of LRP1 deletion in vascular mural cells and APOE gentotype on gene expression in mouse brains

Project description:To investigate the apoE isoform-dependent role of vascular mural cell (VMC)-LRP1, we generated VMC-specific LRP1 knockout mice (smLrp1-/-), followed by breeding these mice with either APOE3-targeted replacement (TR) or APOE4-TR mice We then performed gene expression profiling analysis using data obtained from RNA-seq of cortical samples from 4 different mouse models

2023-05-12 | GSE225065 | GEO

The TIMP3/Apelin axis Regulates Atherosclerosis and Heart Metabolism leading to increased mortality in ApoE null Mice

Project description:The role of TIMP3 in the context of cardiovascular remodeling is relatively unexplored when considering classical risk factors such as hypercholesterolemia, diabetes and hypertension. To learn more the role of TIMP3 in the progression of cardiovascular disease we combined genetics, metabolomics and in vivo phenotypical analysis using the hypercholesterolemic ApoE null mice to generate ApoE-/-Timp3-/- mice, the latter showing increased atherosclerosis, increased mortality and arrhythmias compared to ApoE-/- mice. We have previously described Timp3-/-mice in ( Fiorentino, L., et al., Regulation of TIMP3 in diabetic nephropathy: a role for microRNAs. Acta Diabetol, 2013) . To generate ApoE-/-Timp3-/- knockout animals we crossbred the 2 strains. Offsprings were then backcrossed into ApoE animals for 6 generations to generate a pure lineage. Collectively, metabolite profiles, gene and protein expression consistently suggested a role for TIMP3 to underlie a decreased activation of PPARα/AMPK to dampen fatty acids β-oxidation eventually leading to atherosclerotic plaque composition vulnerability and perturbation of heart metabolism. mRNA profiling in ApoE-/-Timp3-/- mice revealed a TIMP3 effect to regulate Apelin, which we found decreased in the circulation due to its specific downregulation at the myocardial level but not in other well known sites of expression such as the adipose tissue. mRNA sequencing of the heart of ApoE-/-Timp3-/- mice vs ApoE-/- littermates controls.

2015-01-01 | E-GEOD-53548 | biostudies-arrayexpress

Model of heart failure induced by mild thiol-blocking with cystamine

Project description:Depletion of cardiac ATP content is a characteristic feature of heart failure in patients and experimental animal models. To analyze the impact of insufficient ATP supply on heart function we inhibited cellular respiration by disulfide poisoning with the mild thiol-blocking agent, cystamine. We chose 4 month-old apolipoprotein E (apoE)-deficient mice, which are highly vulnerable to increased oxygen and ATP demands. After 4 weeks of cystamine treatment (300 mg/kg in drinking water), echocardiography and histology analyses demonstrated that apoE-deficient mice had developed heart failure with cardiac dilation. The microarray gene expression study of heart tissue from cystamine-treated apoE-deficient mice relative to untreated mice confirmed the development of heart failure showing up-regulation heart failure-specific genes by mild thiol-blocking with cystamine. Microarray gene expression profiling was performed with heart tissue isolated from three study groups: (i) cystamine-treated 5 month-old apolipoprotein- (apoE)- deficient mice with symptoms of heart failure, (ii) untreated 5 month-old apoE- deficient mice, and (iii) age-matched, untreated, non-transgenic B6 control mice.

2010-12-03 | E-GEOD-25768 | biostudies-arrayexpress

Cardiac gene expression profiling of apoE-deficient mice receiving heart failure treatment with the anti-ischemic drug ranolazine

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

ABCA1 haplodeficiency affects the brain transcriptome following traumatic brain injury in mice expressing human APOE isoforms

Project description:We examined the impact of Abca1 deficiency and APOE isoform expression on the response to TBI using 3-months-old, human APOE3+/+ (E3/Abca1+/+) and APOE4+/+ (E4/Abca1+/+) targeted replacement mice, and APOE3+/+ and APOE4+/+ mice with only one functional copy of the Abca1 gene (E3/Abca1+/-; E4/Abca1+/-). TBI-treated mice received a craniotomy followed by a controlled cortical impact (CCI) brain injury in the left hemisphere; sham-treated mice received the same surgical procedure without the impact. We performed RNA-seq using samples from cortices and hippocampi collected at 14 days post-injury, followed by genome-wide differential gene expression analysis.

2018-07-31 | GSE117223 | GEO

Differential gene expression in APOE3 and APOE4 gene targeted replacement mice

Project description:The aim of the study was to investigate hepatic gene expression profiles differentially regulated by the APOE genotype in gene targeted replacement mice. The APOE4 genotype is associated with increased mortality in the elderly and is an independent risk factor for age-dependent chronic diseases. However, little is known about the underlying mechanisms and molecular targets involved in the APOE4-risk association. As APOE is centrally involved in lipid and cholesterol metabolism and in large part is produced in the liver, we analyzed hepatic RNA profiles of APOE4- and APOE3-expressing mice.

2012-12-15 | GSE42930 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data