Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA122207 | 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:Gene expression analysis of cardiac left-ventricle tissue from hybrid mice harboring the Scn5a-1798insD/+ mutation
| PRJNA137487 | 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: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:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility.
2014-12-04 | GSE61417 | GEO
Project description: Not available
| S-EPMC8784167 | biostudies-literature
Project description:Particulate Matter effect on Mouse Model of Cardiac Failure: Lung and Heart Left Ventricle
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Project description:Arterial pulmonary hypertension is a rare disease, with little knowledge regarding its etiology, and high mortality. Development of right and later on also left ventricular heart insufficiency, secondary to pulmonary hypertension, is a negative predictive factor. Genetic and molecular processes underlying left heart ventricle remodeling over the course of pulmonary hypertension remain unknown. In particular, there is no knowledge regarding the mechanisms of left heart ventricle atrophy which was completely avoided by researchers until recently.The aim of this study was to assess changes in protein abundance in left and right heart ventricle free wall of rats in monocrotaline model of PAH.
2020-09-07 | PXD015896 | Pride
Project description:A comparison of human cardiac gene expression profile in paired samples of right atrium and left ventricle extracted in vivo<br><br>
2012-01-30 | E-MEXP-3396 | biostudies-arrayexpress
Project description:Expression Profiling of Dll1 mutant mouse lines on different genetic background
| PRJNA105675 | ENA