expression profile of conditional knock out of beta-catenin by K19-CRE at E7.5. Tested a wild type with two alleles of beta-catenin, a heterzyote with one deleted allele and the conditional null in the domain on cytokeratin 19 driven CRE expression
Dissecting Wnt/beta-catenin signaling during gastrulation using RNA interference in mouse embryos.
No sample metadata fields
View SamplesDefective insulin secretion by pancreatic ß cells underlies the development of type 2 diabetes (T2D). High fat diet-fed mice are commonly used to study diabetes progression, but studies are usually limited to a single strain, such as C57Bl/6J. Here, we use a systems biology approach to integrate large phenotypic and islet transcriptomic data sets from six commonly used strains fed a high fat or regular chow diet to identify genes associated with glucose intolerance and insulin secretion. One of these genes is Elovl2, encoding very long chain fatty acid elongase 2. ELOVL2 is responsible for the synthesis of the polyunsaturated fatty acid, docosahexaenoic acid (DHA). We show that DHA rescues glucose-induced insulin secretion and cytosolic Ca2+ influx impaired by glucolipotoxicity, and that Elovl2 over-expression is able to restore the insulin secretion defect under these conditions. We propose that increased endogenous DHA levels resulting from Elovl2 up-regulation counteracts the insulin secretion defect associated with glucolipotoxicity. Although we focus our experimental validation on Elovl2, the comprehensive data set and integrative network model we used to identify this candidate gene represents an important novel resource to dissect the molecular aetiology of ß cell failure in murine models. Overall design: 6 mouse strains, 4 time points, 2 diets
Molecular phenotyping of multiple mouse strains under metabolic challenge uncovers a role for <i>Elovl2</i> in glucose-induced insulin secretion.
Specimen part, Cell line, Subject, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Atrial identity is determined by a COUP-TFII regulatory network.
Age, Specimen part
View SamplesAtria and ventricles exhibit distinct molecular profiles that produce structural and functional differences between the two cardiac compartments. However, factors that determine these differences remain largely undefined. Cardiomyocyte-specific COUP- TFII ablation produces ventricularized atria that exhibit ventricle-like action potentials, increased cardiomyocyte size, and development of extensive T-tubules.
Atrial identity is determined by a COUP-TFII regulatory network.
Age, Specimen part
View SamplesWe sequenced mRNA from Left Ventricles of Streptozotocin induced Type I diabetic mouse hearts or mock treated controls at 4 weeks post-treatment in order to assess alternative splicing changes. Overall design: Heart mRNA profiles of Control and Diabetic (STZ:T1D) mice were generated by deep sequencing using Illumina HiSeq 1000.
Dysregulation of RBFOX2 Is an Early Event in Cardiac Pathogenesis of Diabetes.
Age, Specimen part, Cell line, Treatment, Subject
View SamplesGene expression in forebrain structures change during day and night depending on circadian and rest-activity cycles. Clock genes have been shown to be involved in the control of circadian and sleep-wake control.
Mice lacking the circadian modulators SHARP1 and SHARP2 display altered sleep and mixed state endophenotypes of psychiatric disorders.
Age, Specimen part, Time
View SamplesHigh-throughput sequencing of mRNA from mouse lung infected with 1918 pandemic influenza virus revealed that reactive oxygen species scavenger EUK-207 treatment resulted in decreased expression of inflammatory response genes and increased lung metabolic and repair responses.
Treatment with the reactive oxygen species scavenger EUK-207 reduces lung damage and increases survival during 1918 influenza virus infection in mice.
No sample metadata fields
View SamplesThe association between chronic inflammation and the development and progression of malignancy is exemplified in the biliary tract where persistent inflammation strongly predisposes to cholangiocarcinoma. The inflammatory cytokine interleukin-6 (IL-6) enhances tumor growth in cholangiocarcinoma by altered gene expression via autocrine mechanisms. We therefore investigated the effect of chronic exposure to IL-6 on gene expression using malignant cholangiocytes stably transfected to overexpress IL-6. Comparison of gene expression identified several genes that were altered by enforced IL-6 expression.
Interleukin-6 contributes to growth in cholangiocarcinoma cells by aberrant promoter methylation and gene expression.
No sample metadata fields
View SamplesUse of archival resources has been limited to date by inconsistent methods for genomic profiling of degraded RNA from formalin-fixed paraffin-embedded (FFPE) samples. RNA-seq offers a novel way to address this problem. In this study we evaluated transcriptomic dose responses using RNA-seq in paired FFPE and frozen (FROZ) samples from two archival studies in mice, one recent (<2 years old) and the other older (>20 years old). Experimental treatments included di(2-ethylhexyl)phthalate (DEHP) and dichloroacetic acid (DCA) for the <2 and >20 year-old studies, respectively. Total RNA was ribodepleted and sequenced using the Illumina HiSeq platform. In the recent study, FFPE samples showed high concordance in total reads (98% vs FROZ), fold-change values of differentially expressed genes (DEGs) (R2 = 0.99), highly enriched target pathways (90% overlap with FROZ), and benchmark dose estimates for preselected target genes (-2% overall vs FROZ). In contrast, RNA-seq data from older FFPE samples had lower total reads (70% vs FROZ) and poor concordance in global DEGs and pathways. Despite a 99% loss of counts, dose responses were still evident for target genes in FFPE samples and positively correlated with paired FROZ samples. These findings highlight potential variability in the quality of RNA-seq data from FFPE samples. More recent FFPE samples were highly similar to FROZ samples in sequencing quality metrics, DEG profiles, and dose-response parameters, while further methods development is needed for older or lower-quality FFPE samples. This work should help broaden the use of archival resources in both chemical safety and translational science. Overall design: Trancriptomic profiles obtained using from paired frozen (FROZ) and formalin-fixed paraffin-embedded (FFPE) liver samples collected in 2013 for the DEHP study (n=16 FROZ, n=16 FFPE, with four dose groups at 0, 1500, 3000, and 6000 ppm DEHP, n=4 per dose group) and 1994 for the DCA study (n=24 FROZ, n=24 FFPE, with four dose groups at 0, 1.0, 2.0, and 3.5 g/L DCA, n=6 per dose group) using Illumina HiSeq platform.
Editor's Highlight: Dose-Response Analysis of RNA-Seq Profiles in Archival Formalin-Fixed Paraffin-Embedded Samples.
Sex, Age, Specimen part, Cell line, Treatment, Subject
View SamplesJak1 is a ubiquitously expressed tyrosine kinase that transduces extracellular signals from a variety of cytokines and their receptors to downstream signal transducers and activators of transcription (STATs). Since deficiency in Jak1 causes early neonatal lethality, we generated Jak1 conditional knockout mice to study the biological role of this kinase during the development of the mammary gland in adult females Overall design: Total RNA was extracted from flash-frosen mammary gland tissues of seven conditional knockout females(3 lactation, 4 second day of involution) and six wildtype control mice(3 lactating, 3 involution)
Janus Kinase 1 Is Essential for Inflammatory Cytokine Signaling and Mammary Gland Remodeling.
Specimen part, Subject
View Samples