Project description:Purpose: Transcriptome profiling (RNA-seq) to microarray to evaluate transcriptional changes in the heart of HD mouse models Methods: Heart mRNA profiles of 4-weeks-old wild-type (WT) and R6/2 transgenic; 15-weeks-old WT and R6/2 transgenic mice; 8-month-old WT and HdhQ150 knock-in mice; 22-month-old WT and HdhQ150 knock-in mice were generated by deep sequencing, in triplicate, using Illumina Hi-seq 2000. Conclusions: Our study showed that there is no major transcriptional deregulation in the heart of mouse models of HD.
Project description:Purpose: Transcriptome profiling (RNA-seq) to microarray to evaluate transcriptional changes in the heart of HD mouse models Methods: Heart mRNA profiles of 4-weeks-old wild-type (WT) and R6/2 transgenic; 15-weeks-old WT and R6/2 transgenic mice; 8-month-old WT and HdhQ150 knock-in mice; 22-month-old WT and HdhQ150 knock-in mice were generated by deep sequencing, in triplicate, using Illumina Hi-seq 2000. Conclusions: Our study showed that there is no major transcriptional deregulation in the heart of mouse models of HD. Heart mRNA profiles of 4-weeks-old wild-type (WT) and R6/2 transgenic; 15-weeks-old WT and R6/2 transgenic mice; 8-month-old WT and HdhQ150 knock-in mice; 22-month-old WT and HdhQ150 knock-in mice were generated by deep sequencing, in triplicate, using Illumina Hi-seq 2000.
Project description:Analysis of transcriptome of prostate tissue from the anterior lobe or tumor from 9, 12, 13, 14, and 16 months old mouse Prostate tissue or tumor from 9 month old Nkx3.1CreERT2/+ mice, 14 month old Nkx3.1CreERT2/+;Ptenflox/flox mice (intact, treated with vehicle), 16 month old Nkx3.1CreERT2/+;Ptenflox/flox mice (castrated, treated with vehicle or abiraterone), 12 month old Nkx3.1CreERT2/+;Ptenflox/flox;P53flox/flox mice(intact, treated with vehicle), 13 month old Nkx3.1CreERT2/+;Ptenflox/flox;P53flox/flox mice (castrated, treated with vehicle or abiraterone) was harvested, and snap frozen for subsequent molecular analysis
Project description:The heart proteome and phosphoproteome were analyzed in young (5-6-month old), old (24-month old at the start of the study), and elamipretide-treated (for 8 weeks) old mice using shotgun proteomics methods in order to assess the effects of aging on signaling and the ability of mitochondrion-targeted drug elamipretide (SS-31) to reverse age-related changes. Enhancement and suppression of phosphorylation at sites along a variety of proteins was found to occur with age. Elamipretide treatment partially restored the phosphorylation state of proteins that had increased phosphorylation with age, but did not have a large effect those that had decreased phosphorylation with age.
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.
Project description:Analysis of transcriptome from 12 month old finasteride (and vehicle) treated mouse prostatic tissue Prostate tissue from 12 month old Nkx3.1+/+ and Nkx3.1-/- mice treated with finasteride (or vehicle) was harvested, and snap frozen for subsequent molecular analysis
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.
Project description:The anti-diabetic drug and agonist of the peroxisome proliferator-activated receptor gamma (Pparg), rosiglitazone, was recently withdrawn in many countries because the drug use was associated with an increased risk of heart failure. To investigate underlying pathomechanisms, we chose 6-month-old apolipoprotein E (apoE)-deficient mice, which are prone to atherosclerosis and insulin resistance, and thereby mimic the risk profile of patients with cardiovascular disease. After 8 weeks of rosiglitazone treatment (30 mg/kg/day), echocardiography and histology analyses demonstrated that rosiglitazone had induced heart failure with cardiac dilation. Concomitantly, cardiac lipid overload and lipid-induced cardiomyocyte death developed. The microarray gene expression study of heart tissue from rosiglitazone-treated apoE-deficient mice relative to untreated apoE-deficient mice and non-transgenic B6 mice identified cardiac Pparg-dependent lipid metabolism genes in rosiglitazone-treated mice, which seem to trigger a major heart failure promoting pathway. Microarray gene expression profiling was performed with heart tissue isolated from three study groups: (i) rosiglitazone-treated 8-month-old apolipoprotein (apoE)-deficient mice with symptoms of heart failure, (ii) untreated 8-month-old apoE-deficient mice, and (iii) age-matched, untreated, non-transgenic B6 control mice.
Project description:We performed an RNA Sequencing experiment on dorsal hippocampal tissue from six groups of animals: Aging (18-20-month-old) HDAC3flox/flox homecage (H3F-HC); Aging (18-20-month-old) HDAC3flox/flox 60min post training (H3F-BV); Aging (18-20-month-old) wildtype homecage (OWT-HC); Aging (18-20-month-old) wildtype 60min post training (OWT-BV); Young (2-4-month-old) wildtype homecage (YWT-HC); Young (2-4-month-old) wildtype 60min post training (YWT-BV). Homecage animals were sacrificed directly from the animal's cage. Behavior animals were sacrificed sixty minutes following a 10min Object Location Memory training session.
