Developmental gene expression differences between neonatal and adult mouse atria and ventricles
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ABSTRACT: We study the role of glycosylation in ion channel function. Specfically, we are focusing on how ion channel glycosylation modulates, controls, and impacts cardiac, skeletal muscle, and neuronal electrical activity. We wish to determine differences in gene expression through development and between the atria and ventricles of the mouse heart. Our data indicate differential sialylation directly affects voltage-gated sodium channel function through the developing heart in a chamber-specific manner. We wish to expand our findings to include other ion channels involved in the cardiac action potential, and to eventually create a map of the cardiac conduction system that details the role of differential glycosylation in cardiac excitability. Determining differential expression of the genes that regulate ion channel glycosylation is vital to these goals. We analyzed four sets of pooled RNA to be run in triplicate: one each from neonatal and adult mouse atria and ventricles.
Project description:We study the role of glycosylation in ion channel function. Specfically, we are focusing on how ion channel glycosylation modulates, controls, and impacts cardiac, skeletal muscle, and neuronal electrical activity. We wish to determine differences in gene expression through development and between the atria and ventricles of the mouse heart. Our data indicate differential sialylation directly affects voltage-gated sodium channel function through the developing heart in a chamber-specific manner. We wish to expand our findings to include other ion channels involved in the cardiac action potential, and to eventually create a map of the cardiac conduction system that details the role of differential glycosylation in cardiac excitability. Determining differential expression of the genes that regulate ion channel glycosylation is vital to these goals.
Project description:Expression level, control and intercoordination of 66 selected heart rhythm determinant (HRD) genes were compared in atria and ventricles of 4 male and 4 female adult mice. We found that genes encoding various adrenergic receptors, ankyrins, ion channels and transporters, connexins and other components of the intercalated discs form a complex network that is chamber dependent and differs between the two sexes. In addition, most HRD genes in atria had higher expression in males than in females, while in ventricles expression levels were mostly higher in females than in males. Moreover, significant chamber-differences were observed between the sexes, with higher expression in atria than ventricles for males and higher expression in ventricles than atria for females. We have ranked the selected genes according to their prominence in controlling the HRD gene web through expression coordination with the other web genes and protecting the web though their own expression stability. Interestingly, the prominence hierarchy was substantially different between the two sexes. Taken together these findings indicate that the organizational principles of the heart rhythm transcriptome are sex-dependent, with the newly introduced prominence analysis allowing identification of genes that are pivotal for the sexual dichotomy.
Project description:Pharmacological and gene ablation studies have demonstrated a crucial role of the cardiac natriuretic peptides (NP) hormones ANF and BNP in the maintenance of cardiovascular homeostasis. In addition, hypertension and chronic congestive heart failure are clinical entities that may be regarded as states of relative NP deficiency. Hence the study of the function of the endocrine heart is highly relevant. To identify genes that are related to the endocrine function of the heart we have conducted differential gene expression studies of the rat atria and ventricles using oligonucleotide arrays. Keywords: comparative genomic hybridization
Project description:Previous epidemiological studies have shown that males tend to have an increased overall lifetime risk of developing atrial fibrillation (AF), whereas females tend to be more susceptible to the development of ventricular tachyarrhythmias resulting from long-QT syndrome and drug-induced Torsades de Pointes. In this study, we compared the transcript-level expression of 89 ion channel subunits, calcium handling proteins, and other transcription factors in the left atria (LA) and ventricles (LV) of human hearts of both genders.
Project description:Atria 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. We used microarrays to examine the molecular profile of cardiomyocyte-specific COUP-TFII knockout adult atria in comparison with that of normal atria. We extracted RNA from mutant right atria, control right atria and control ventricles from 2 months old adult mice, followed by gene expression profiling using Affymetrix microarrays.
Project description:Expression level, control and intercoordination of 66 selected heart rhythm determinant (HRD) genes were compared in atria and ventricles of 4 male and 4 female adult mice. We found that genes encoding various adrenergic receptors, ankyrins, ion channels and transporters, connexins and other components of the intercalated discs form a complex network that is chamber dependent and differs between the two sexes. In addition, most HRD genes in atria had higher expression in males than in females, while in ventricles expression levels were mostly higher in females than in males. Moreover, significant chamber-differences were observed between the sexes, with higher expression in atria than ventricles for males and higher expression in ventricles than atria for females. We have ranked the selected genes according to their prominence in controlling the HRD gene web through expression coordination with the other web genes and protecting the web though their own expression stability. Interestingly, the prominence hierarchy was substantially different between the two sexes. Taken together these findings indicate that the organizational principles of the heart rhythm transcriptome are sex-dependent, with the newly introduced prominence analysis allowing identification of genes that are pivotal for the sexual dichotomy. Four adult male (M) and 4 adult female (F) mice were decapitated, the hearts removed and atria (A) and ventricles (V) collected in separate tubes. 20 µg total RNA extracted in Trizol from each of the 16 samples was reverse transcribed in the presence of fluorescent Alexa Fluor®_647 and Alexa Fluor®_555-aha-dUTPs (Invitrogen, CA) to obtain labeled cDNAs Red and green-labeled samples of biological replicas were then co-hybridized (âmultiple yellowâ strategy) overnight at 50°C with mouse MO36k oligonucleotide arrays printed by Duke University (http://microarray.genome.duke.edu/spotted-arrays) with Operon Mouse Oligo Set, version 4.0. After washing (0.1% SDS and 1% SSC) to remove the non-hybridized cDNA, each array was scanned with GenePix 4000B scanner (MDS, Toronto, Canada) and images were primarily analyzed with GenePixPro 6.0 (Axon Instruments, CA).
Project description:Pharmacological and gene ablation studies have demonstrated a crucial role of the cardiac natriuretic peptides (NP) hormones ANF and BNP in the maintenance of cardiovascular homeostasis. In addition, hypertension and chronic congestive heart failure are clinical entities that may be regarded as states of relative NP deficiency. Hence the study of the function of the endocrine heart is highly relevant. To identify genes that are related to the endocrine function of the heart we have conducted differential gene expression studies of the rat atria and ventricles using oligonucleotide arrays. Experiment Overall Design: The atrial appendages and the ventricular free walls were obtained from thirteen normal male Sprague Dawley rats. The total RNA was obtained from four pools of atrial and four pools of ventricular tissues. Four biological replicates for each muscle type were generated, i.e. 4 atrial replicates and 4 ventricular replicates.
Project description:In this study, we have identified MEF2A-sensitive genes in atrial and ventricular chambers of the adult heart. MEF2A is a member of the myocyte enhancer factor 2 (MEF2) family of transcription factors. MEF2 proteins are expressed in skeletal and cardiac muscle tissues and are conserved across many mammalian species, but the gene programs regulated by MEF2A in adult cardiac chambers are largely unknown. We compared gene expression profiles between WT and Mef2a knockout atria and ventricles from adult mice, and the results identified distinct and overlapping sets of genes sensitive to the loss of MEF2A in the adult heart.
Project description:Atria 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. We used microarrays to examine the molecular profile of cardiomyocyte-specific COUP-TFII knockout adult atria in comparison with that of normal atria.