Project description:Tumor Necrosis Factor-α is greatly implicated in heart pathophysiology, while it is upregulated in the failing myocardium. A major target in TNF-α-induced heart failure is the muscle specific intermediate filament cytoskeleton, comprised by desmin. We analysed the effect of cardiac-specific overexpression of TNF-α in the Des-/- myocardium, which is a known model of dilated cardiomyopathy. Hearts of 3 months old mice (n=3) of Des-/- and TNFαDes-/- genotypes were used for whole genome microarray hybridization analysis.
Project description:Tumor Necrosis Factor-α is greatly implicated in heart pathophysiology, while it is upregulated in the failing myocardium. A major target in TNF-α-induced heart failure is the muscle specific intermediate filament cytoskeleton, comprised by desmin. We analysed the effect of cardiac-specific overexpression of TNF-α in the Des-/- myocardium, which is a known model of dilated cardiomyopathy.
Project description:DES is a synthetic estrogen that is associated with adverse effects on reproductive organs. Our group has employed estrogen receptor (ER) α knockout (αERKO) mice to gain insight into the contribution of ER α in DES-induced toxicity following neonatal exposure
Project description:DES is a synthetic estrogen that is associated with adverse effects on reproductive organs. Our group has employed estrogen receptor (ER) α knockout (αERKO) mice to gain insight into the contribution of ER α in DES-induced toxicity following neonatal exposure
Project description:The pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-α), has been suggested to be a key factor in the induction of obesity-associated metabolic dysfunction. However, the role that macrophage-derived TNF-α has on regulating metabolic perturbations in obesity is not completely understood. Therefore, we utilized the TNF-αFlox/FLox (F/F), LyzMcre+/- mouse model to determine the impact that macrophage TNF-α deletion has on the development of high-fat-diet (HFD)-induced obesity.
Project description:DES is a synthetic estrogen that is associated with adverse effects on reproductive organs. Our group has employed estrogen receptor (ER) α knockout (αERKO) mice to gain insight into the contribution of ER a in DES-induced toxicity following neonatal exposure.
Project description:DES is a synthetic estrogen that is associated with adverse effects on reproductive organs. Our group has employed estrogen receptor (ER) α knockout (αERKO) mice to gain insight into the contribution of ER a in DES-induced toxicity following neonatal exposure.
Project description:DES is a synthetic estrogen that is associated with adverse effects on reproductive organs. Our group has employed estrogen receptor (ER) α knockout (αERKO) mice to gain insight into the contribution of ER-dependent pathways in mediating the effects of neonatal DES exposure in female and male reproductive tract tissues. The objective of this study is to compare gene expression profiles between the WT-veh and -DES groups or αERKO-veh and -DES from the adult male mice (week 10) of the SV tissues to identify differential genes.
Project description:Abstract. Very little is known regarding how hormonal exposures impact the epigenetic landscape of developing tissues in the context of a whole organism, in contrast to the impact on cultured cells. Here we took a global approach to understanding how neonatal exposure to the xenoestrogen, diethylstilbestrol (DES), alters the uterine epigenome. RNA-seq and ChIP-seq (H3K4me3, H3K27me3, H3K27ac and H3K4me1) were performed on DES-treated and control uteri. The most striking finding was differential association of H3K27ac and H3K4me1 at typical and super-enhancer regions of 79% of altered genes. These peaks overlapped with previously reported estrogen receptor a (ERα) ChIP-seq peaks. Conditional uterine deletion of ERα (Esr1cKO) conferred protection of 88% of altered genes. H3K27ac ChIP-seq on Esr1cKO samples showed that 72% of protected genes had a differential H3K27ac enhancer. These data suggest that DES regulates gene expression in the neonatal mouse uterus by H3K27ac association at ERα binding sites near estrogen-regulated genes.
