Project description:The AE3 (Slc4a3) Cl/HCO3 exchanger is highly abundant in heart, but its function is not known. To assess its function we performed RNA Seq analysis of mRNA from hearts of AE3-null and wild-type mice. The patterns of differential gene expression indicate mild hypoxia, enhanced glucose metabolism, and reduced fatty acid metabolism in cardiac myocytes, which is consistent with the hypothesis that HCO3 extrusion by AE3 plays a role in carbon dioxide disposal.
Project description:As Grl/Hey2 directly binds DNA through E box motifs and mediates transcription repression, we aim to gain insights into potential target genes of Grl/Hey2 during heart regeneration. We performed RNA-seq analyses using total RNAs collected from 4-HT-treated Tg(cmlc2:creER;cmlc2:nRSGG) hearts and Tg(cmlc2:nRSGG) control hearts, as well as grl5nt-/- mutant hearts and wild-type hearts following ventricular resection at 7 dpa. Using RNA profile analyses, we have identified some potential genes act downstream of Grl/Hey2-dependent transcriptional repression during heart regeneration.
Project description:This experiment aimed to investigate the transcriptional role of G4 resolvase Dhx36 in the adult mouse heart. We compared three pools of wild-type (WT) mouse hearts with three pools of Dhx36 conditional knockout (cKO) hearts. In the mutant mice, Dhx36 was conditionally deleted in cardiomyocytes using the Myh6-cre transgenic line. Each of the six pools was created using RNA extracted from 3-5 hearts from mice aged approximately 21 days. The cKO mice developed dilated cardiomyopathy and began experiencing sudden death at 40 days old, with no mutants surviving beyond 5 months.
Project description:Mice lacking the zinc finger transcription factor Specificity protein 3 (Sp3) die prenatally in the C57Bl/6 background. To elucidate the cause of mortality we analyzed the potential role of Sp3 in embryonic heart development. Sp3 null hearts display defective looping at E10.5, and at E14.5 the Sp3 null mutants have developed a range of severe cardiac malformations. In an attempt to position Sp3 in the cardiac developmental hierarchy, we analysed the expression patterns of >15 marker genes in Sp3 null hearts. Expression of Cardiac ankyrin repeat protein (Carp) was downregulated prematurely after E12.5, while expression of the other marker genes was not affected. ChIP analysis revealed that Sp3 is bound to the Carp promoter region in vivo. Microarray analysis indicates that small molecule metabolism and cell-cell interactions are the most significantly affected biological processes in E12.5 Sp3 null myocardium. Since the epicardium showed distension from the myocardium, we studied expression of Wt1, a marker for epicardial cells. Wt1 expression was diminished in epicardium-derived cells in the myocardium of Sp3 null hearts. We conclude that Sp3 is required for normal cardiac development, and suggest that it has a crucial role in myocardial differentiation. ( Keywords: Transcription factors, Sp3, knockout mice, cardiac malformations, E12.5
Project description:CCBE1 is a secreted extracellular matrix protein expressed by epicardial cells but its role during epicardial development was still unknown.Using a Ccbe1 knockout (KO) mouse model, we observed that loss of CCBE1 leads to congenital heart defects including thinner and hyper-trabeculated ventricular myocardium. In addition, Ccbe1 mutant hearts displayed reduced proliferation of cardiomyocyte and epicardial cells. RNA-seq data of CCBE1 KO and WT murine hearts indicated deregulation of genes associated with development and morphogenesis including the epithelial-to-mesenchymal transition.
Project description:Total RNA was isolated from 3 WT and 3 ERRa null hearts and independent hybridizations were performed using MOE430 2.0 microarrays. Expression profiling was conducted to determine changes in gene expression in hearts lacking ERRa. The expression of genes involved in heart and muscle development, muscle contraction, lipid metabolism, OxPhos, protein metabolism and transcription were affected by the loss of ERRa. Keywords: microarray and genetic modification
Project description:The Carbohydrate Responive Element Binding Protein (ChREBP) is a transcription factor sensing glucose. Two isoforms are produced by the same gene, the long isoform ChREBPalpha and the short one ChREBPbeta transcribed from an alternative promoter. ChREBPalpha activates transcription of ChREBPbeta in response to glucose. The latter is thought to mediate most of the ChREBP transcriptional activation of target genes. However, the contribution of ChREBPbeta in metabolic adaptations in vivo is not known. This study aims at dertermining the contribution of the short isoform ChREBPbeta to the changes in gene expression mediated by ChREBP.
