Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA137487 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Prolonged electrocardiographic indices reflecting myocardial impulse conduction and repolarization are risk factors for sudden cardiac death and drug-induced arrhythmia. The PR-interval, QRS-duration and QT-interval are heritable traits influenced by multiple genetic and environmental factors. The genetic underpinnings of these traits are still largely unknown. In this study, we leveraged the variability in cardiac gene expression and the variation in PR-, QRS- and QT-intervals among F2 mice harboring the cardiac sodium ion-channel mutation Scn5a-1798insD/+ derived from the 129P2-Scn5a1798insD/+ and FVB/NJ-Scn5a1798insD/+ cross, to isolate novel genes and biological pathways impacting on cardiac conduction and repolarization. Cardiac left-ventricle total RNA from 120 F2-(129P2xFVBN/J)-Scn5a-1798insD/+ mice at 12 to 14 weeks old.
2012-12-01 | E-GEOD-27236 | biostudies-arrayexpress
Project description:Prolonged electrocardiographic indices reflecting myocardial impulse conduction and repolarization are risk factors for sudden cardiac death and drug-induced arrhythmia. The PR-interval, QRS-duration and QT-interval are heritable traits influenced by multiple genetic and environmental factors. The genetic underpinnings of these traits are still largely unknown. In this study, we leveraged the variability in cardiac gene expression and the variation in PR-, QRS- and QT-intervals among F2 mice harboring the cardiac sodium ion-channel mutation Scn5a-1798insD/+ derived from the 129P2-Scn5a1798insD/+ and FVB/NJ-Scn5a1798insD/+ cross, to isolate novel genes and biological pathways impacting on cardiac conduction and repolarization.
2012-12-01 | GSE27236 | GEO
Project description:Left ventricular hypertrabeculation (LVHT) is a heterogenous cardiac condition with a complex and poorly understood aetiology. We comprehensively characterised the effect of a novel P1891A mutation in the SCN5A gene, which encodes for the voltage gated sodium channel Nav1.5, identified in a Finnish family diagnosed with LVHT.
2024-08-29 | MSV000095720 | MassIVE
Project description:Genetic background effect on Scn5a mutant cardiac right ventricle gene expression
| PRJNA122207 | ENA
Project description:Conduction slowing of the electric impulse that drives the heartbeat may evoke lethal cardiac arrhythmias. Mutations in SCN5A, which encodes the pore-forming cardiac sodium channel alpha subunit, are associated with familial arrhythmia syndromes based on conduction slowing. However, disease severity among mutation carriers is highly variable. We hypothesized that genetic modifiers underlie the variability in conduction slowing and disease severity. With the aim of identifying such modifiers, we studied the Scn5a(1798insD/+) mutation in 2 distinct mouse strains, FVB/N and 129P2. In 129P2 mice, the mutation resulted in more severe conduction slowing particularly in the right ventricle (RV) compared to FVB/N. Pan-genomic mRNA expression profiling in the 2 mouse strains uncovered a drastic reduction in mRNA encoding the sodium channel auxiliary subunit beta4 (Scn4b) in 129P2 mice compared to FVB/N. This corresponded to low to undetectable beta4 protein levels in 129P2 ventricular tissue, whereas abundant beta4 protein was detected in FVB/N. Sodium current measurements in isolated myocytes from the 2 mouse strains indicated that sodium channel activation in myocytes from 129P2 mice occurred at more positive potentials compared to FVB/N. Using computer simulations, this difference in activation kinetics was predicted to explain the observed differences in conduction disease severity between the 2 strains. In conclusion, genetically determined differences in sodium current characteristics on the myocyte level modulate disease severity in cardiac sodium channelopathies. In particular, the sodium channel subunit beta4 (SCN4B) may constitute a potential genetic modifier of conduction and cardiac sodium channel disease.
2010-01-12 | GSE19741 | GEO
Project description:Female mice aged 6-7 weeks old were infected with the T. cruzi H1 strain. Mice were randomly divided into groups with 15 animals in each, with age matched naïve mice included as controls. Approximately 75 days post infection, mice were randomly divided into groups and treated with different treatment combinations: BNZ + Tc24 therapeutic vaccine + the STAT-3 inhibitor TTI-101, BNZ + Tc24 vaccine, and BNZ or TTI alone. Mice were humanely euthanized at 50, 75, 120 or 142 days post infection (DPI), and hearts samples were collected, divided into left atrium (LA), right atrium (RA), left ventricle top (LVT), left ventricle bottom (LVB), right ventricle top (RVT), right ventricle bottom (RVB). Heart tissue samples were extracted by 1:1 (v/v) methanol to water for aqueous phase and 3:1 (v/v) dichloromethane to methanol for organic phase. LC-MS/MS data acquisition was performed on a Q Exactive Plus Hybrid Quadrupole-Orbitrap Mass Spectrometer coupled to a Thermo Scientific Vanquish UHPLC with 1.7 um 100 Å Kinetex C8 column at 40°C. Mobile phase A was water with 0.1% (v/v) formic acid and mobile phase B was acetonitrile with 0.1% (v/v) formic acid.
2021-05-13 | MSV000087427 | MassIVE
Project description:Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are used to examine in vitro the effect of mutations in the cardiac sodium channel gene SCN5A, associated with cardiac arrhythmias. Postnatally SCN5A undergoes a fetal-to-adult isoform switch, but hiPSC-CMs in conventional 2-dimensional cultures are fetal-like. This impedes evaluation of mutations in the adult isoform. Here, we derived hiPSC-CMs from a patient carrying compound mutations in the adult SCN5A exon 6B and in exon 4 and generated isogenic corrected lines. In hiPSC-CM 2-dimensional culture, exon 6B mutation did not affect single-cell electrophysiology because of its limited expression. CRISPR/Cas9-mediated excision of the fetal exon 6A with did not promote adult SCN5A expression, rather it impaired the splicing. By maturing hiPSC-CMs in three-dimensional tri-cell type cardiac microtissues, SCN5A underwent isoform switch and revealed the functional effect of exon 6B mutation. Upregulation of the splicing factor MBNL1 in hiPSC-CMs either by culture in microtissues or by overexpression was sufficient to promote exon 6B inclusion. Our results support the ability to study developmentally regulated cardiac genes and postnatal cardiac arrhythmias using hiPSC cardiac cells.
2023-05-03 | GSE180290 | GEO
Project description:A comparison of epigenetic nuclear DNA methylation and gene expression changes between human dialated cardiomypathy left ventricle samples and non-failing cardiac left ventricule samples This study addresses how depletion of huaman cardiac left ventricle mitochondrial DNA and epigentic nuclear DNA methylation promote cardiac dysfunction in human dilated cardiomyopathy.
2013-06-05 | GSE43435 | GEO
Project description:High-resolution chromosome conformation capture-sequencing of wildtype mice left ventricle after cardiac stress (i.e. hypertrophy and myocardial infarction)
2021-07-30 | GSE158708 | GEO
Project description:Cigarette smoke (CS) is the major risk factor for COPD and is linked to cardiopulmonary dysfunction. Exercise training, as part of pulmonary rehabilitation, is recommended for all COPD patients. It has several physiological benefits, but the involved mechanisms remain poorly defined. Here, we employed transcriptomic profiling and examined lung endothelium to investigate novel interactions between exercise and CS on cardiopulmonary alterations. Mice were exposed to 20 weeks of CS, CS + 6 weeks of high-intensity interval training on a treadmill or control. Lung and cardiac (left and right ventricle) tissue were harvested, and RNA-sequencing was performed and validated with RT-qPCR. Immunohistochemistry assessed pulmonary arteriolar changes. Transcriptome analysis between groups revealed 37 significantly regulated genes in the lung, 21 genes in the left ventricle, and 43 genes in the right ventricle (likelihood-ratio test). Validated genes that showed an interaction between exercise and CS included angiotensinogen (p=0.002) and resistin-like alpha (p=0.019) in left ventricle, with prostacyclin synthetase different in pulmonary arterioles (p=0.004). Transcriptomic profiling revealed changes in pulmonary and cardiac tissue following exposure to CS, with exercise training exerting rescue effects. Exercise-regulated genes included angiotensinogen and resistin-like alpha. However, it remains unclear if these represent potential candidate genes or biomarkers involved during pulmonary rehabilitation.
2022-11-04 | E-MTAB-12256 | biostudies-arrayexpress