PPARalpha is a ligand-activated transcription factor involved in the regulation of nutrient metabolism and inflammation. Although much is already known about the function of PPARalpha in hepatic lipid metabolism, many PPARalpha-dependent pathways and genes have yet to be discovered. In order to obtain an overview of PPARalpha-regulated genes relevant to lipid metabolism, and to probe for novel candidate PPARalpha target genes, livers from several animal studies in which PPARalpha was activated and/or disabled were analyzed by Affymetrix GeneChips. Numerous novel PPARalpha-regulated genes relevant to lipid metabolism were identified. Out of this set of genes, eight genes were singled out for study of PPARalpha-dependent regulation in mouse liver and in mouse, rat, and human primary hepatocytes, including thioredoxin interacting protein (Txnip), electron-transferring-flavoprotein beta polypeptide (Etfb), electron-transferring-flavoprotein dehydrogenase (Etfdh), phosphatidylcholine transfer protein (Pctp), endothelial lipase (EL, Lipg), adipose triglyceride lipase (Pnpla2), hormone-sensitive lipase (HSL, Lipe), and monoglyceride lipase (Mgll). Using an in silico screening approach, one or more PPAR response elements (PPREs) were identified in each of these genes. Regulation of Pnpla2, Lipe, and Mgll, which are involved in triglyceride hydrolysis, was studied under conditions of elevated hepatic lipids. In wild-type mice fed a high fat diet, the decrease in hepatic lipids following treatment with the PPARalpha agonist Wy14643 was paralleled by significant up-regulation of Pnpla2, Lipe, and Mgll, suggesting that induction of triglyceride hydrolysis may contribute to the anti-steatotic role of PPARalpha. Our study illustrates the power of transcriptional profiling to uncover novel PPARalpha-regulated genes and pathways in liver.
Comprehensive analysis of PPARalpha-dependent regulation of hepatic lipid metabolism by expression profiling.
Sex, Specimen part
View SamplesThe purpose of this study was to characterize the histologic development of OA in a mouse model where OA is induced by destabilization of the medial meniscus (DMM model) and to identify genes regulated during different stages of the disease, using RNA isolated from the joint organ and analyzed using microarrays.427 genes from the microarrays passed consistency and significance filters. There was an initial up-regulation at 2 and 4 weeks of genes involved in morphogenesis, differentiation, and development, including growth factor and matrix genes, as well as transcription factors including Atf2, Creb3l1, and Erg. Most genes were off or down-regulated at 8 weeks with the most highly down-regulated genes involved in cell division and the cytoskeleton. Gene expression increased at 16 weeks, in particular extracellular matrix genes including Prelp, Col3a1 and fibromodulin.The results support a phasic development of OA with early matrix remodelling and transcriptional activity followed by a more quiescent period that is not maintained.
Disease progression and phasic changes in gene expression in a mouse model of osteoarthritis.
Sex, Age, Specimen part
View SamplesFull title: Prepubertal Human Spermatogonia and Mouse Gonocytes Share Conserved Gene Expression of Germline Stem Cell Regulatory Molecules
Prepubertal human spermatogonia and mouse gonocytes share conserved gene expression of germline stem cell regulatory molecules.
Age
View SamplesThe gene expression profile of peripheral Foxp3+ natural regulatory T cells isolated from Foxp3/EGFP bicistronic mice was compared to that of in vitro-induced regulatory T cells and to CD4+ conventional (Foxp3-) T cells. The role of the regulatory T cell transcription factor Foxp3 in shaping the transcriptosomes of natural and induced regulatory T cells was analyzed using mice expressing a mutant FOXP3-EGFP fusion protein (Foxp3deltaEGFP).
A central role for induced regulatory T cells in tolerance induction in experimental colitis.
No sample metadata fields
View SamplesComparative analysis of gene expression in bone marrow-derived macrophages (BMDM) from trsp knockout mice (Trspfl/fl-LysM-Cre+/-) and Control (Trspfl/fl-LysM-Cre-/-) mice.
Selenoproteins regulate macrophage invasiveness and extracellular matrix-related gene expression.
Sex, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Targeted disruption of Hotair leads to homeotic transformation and gene derepression.
Specimen part
View SamplesComparative analysis of gene expression in cultured primary keratinocytes isolated from newborn control (K14-cre; GPx4fl/+) and knockout (K14-cre; GPx4fl/fl) mice.
Targeted disruption of glutathione peroxidase 4 in mouse skin epithelial cells impairs postnatal hair follicle morphogenesis that is partially rescued through inhibition of COX-2.
Specimen part
View SamplesLong noncoding RNAs (lncRNAs) are thought to be prevalent regulators of gene expression, but the consequences of lncRNA inactivation in vivo are mostly unknown. Here we show that targeted deletion of mouse Hotair lncRNA leads to de-repression of hundreds of genes, resulting in homeotic transformation of the spine and malformation of metacarpal-carpal bones. RNA-seq and conditional inactivation reveal an ongoing requirement of Hotair to repress HoxD genes and multiple imprinted loci such as Dlk1-Meg3 and Igf2-H19. Hotair binds to both Polycomb repressive complex 2 that methylates histone H3 at lysine 27 (H3K27) and Lsd1 complex that demethylates histone H3 at lysine 4 (H3K4) in vivo. Hotair inactivation causes coordinate H3K27me3 loss and H3K4me3 gain at select target genes throughout the genome. These results reveal a shared regulatory mechanism to enforce silent chromatin state at Hox and imprinted genes via Hotair lncRNA.
Targeted disruption of Hotair leads to homeotic transformation and gene derepression.
Specimen part
View SamplesTo examine the role of SPS1 in mammals, we generated a Sps1 knockout mouse and found that systemic SPS1 deficiency was embryonic lethal. Embryos were clearly underdeveloped by E8.5 and virtually reabsorbed by E14.5. Removal of Sps1 specifically in hepatocytes using Albumin-cre preserved viability, but significantly affected expression of a large number of mRNAs involved in cancer, embryonic development and the glutathione system. Particularly notable was the extreme deficiency of glutaredoxin 1 (GLRX1) and glutathione-S-transferase omega 1. To assess these phenotypes at the cellular level, we targeted the removal of SPS1 in F9 cells, a mouse embryonal carcinoma cell line, which recapitulated changes in the glutathione system proteins. We further found that several malignant characteristics of SPS1-deficient F9 cells were reversed, suggesting that SPS1 has a role in supporting and/or sustaining cancer. In addition, the increased ROS levels observed in F9 SPS1/GLRX1 deficient cells were reversed and became more like those in F9 SPS1 sufficient cells by overexpressing mouse or human GLRX1. The results suggest that SPS1 is an essential mammalian enzyme with roles in regulating redox homeostasis and controlling cell growth.
Selenophosphate synthetase 1 is an essential protein with roles in regulation of redox homoeostasis in mammals.
Sex, Specimen part
View SamplesComparative analysis of cerebellar gene expression changes occurring in Sca1154Q/2Q and Sca7266Q/5Q knock-in mice
The insulin-like growth factor pathway is altered in spinocerebellar ataxia type 1 and type 7.
Sex, Age
View Samples