Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA183715 | ENA |
REPOSITORIES: ENA
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Project description:Familial hypertrophic cardiomyopathy (FHC) is a disease characterized by ventricular hypertrophy, fibrosis, and aberrant systolic and/or diastolic function. Our laboratories have previously developed 2 mouse models that affect cardiac performance. One transgenic mouse model encodes an FHC-associated mutation in α-tropomyosin (Tm180) that displays severe cardiac hypertrophy with fibrosis and impaired physiological performance. The other model was a gene knockout of phospholamban (PLB), a regulator of calcium uptake in the sarcoplasmic reticulum of cardiomyocytes; the hearts of these mice exhibit hypercontractility with no pathological abnormalities. Previous work in our laboratories show that the hearts of mice that were genetically crossed between the Tm180 and PLB KO mice rescues the hypertrophic phenotype and improves their cardiac morphology and function. We used microarrays to detail the global program of gene expression underlying cardiac remodeling and rescue of the hypertrophic cardiomyopathic phenotype and identified distinct classes of regulated genes during this process. To understand the changes in gene expression that occur over time in these animal models (Tm180, PLB KO, Tm180/PLB KO and nontransgenic control mice), we conducted microarray analyses of left ventricular tissue at 4 and 12 months of age.
2012-12-13 | E-GEOD-42892 | biostudies-arrayexpress
Project description:Familial hypertrophic cardiomyopathy (FHC) is a disease characterized by ventricular hypertrophy, fibrosis, and aberrant systolic and/or diastolic function. Our laboratories have previously developed 2 mouse models that affect cardiac performance. One transgenic mouse model encodes an FHC-associated mutation in α-tropomyosin (Tm180) that displays severe cardiac hypertrophy with fibrosis and impaired physiological performance. The other model was a gene knockout of phospholamban (PLB), a regulator of calcium uptake in the sarcoplasmic reticulum of cardiomyocytes; the hearts of these mice exhibit hypercontractility with no pathological abnormalities. Previous work in our laboratories show that the hearts of mice that were genetically crossed between the Tm180 and PLB KO mice rescues the hypertrophic phenotype and improves their cardiac morphology and function. We used microarrays to detail the global program of gene expression underlying cardiac remodeling and rescue of the hypertrophic cardiomyopathic phenotype and identified distinct classes of regulated genes during this process.
2012-12-13 | GSE42892 | GEO
Project description:Different single mutations on the same sarcomeric gene often cause distinct cardiomyopathy phenotypes as dilated (DCM) or hypertrophic cardiomyopathy (HCM). The key factors involved in this disease divergence is unknown and could be key for disease intervention.We generated isogenic familial DCM and HCM disease-specific human embryonic stem cells (hESCs) carrying the cTnT-DK210 and -DE160 mutation, respectively. Whole transcriptomic RNA-sequencing was used to identify the key gene involved in the earliest disease divergence of cTnT-DK210 caused DCM and cTnT-DE160 caused HCM. Results provide insight into the new molecular mechanisms underlying familial dilated cardiomyopathy.
2021-10-01 | GSE154097 | GEO
Project description:Heart failure with reduced ejection fraction (HFrEF) is a major health problem. Increasing L-type calcium channel (LTCC) activity deteriorates heart function; however, myocardial RRAD knockout (cRADΔ/Δ) instills tonic modulated LTCC current (ICa,L) that preserves healthy myocardium. Thus, we chose to challenge the dogma that enhanced trigger Ca2+ is maladaptive. The study objective was to test the hypothesis that modulated ICa,L in cRADΔ/Δ mice rescues dilated cardiomyopathy by providing tonic modulated trigger Ca2+. Methods and Results Mouse and human models were tested. The muscle lim protein knockout mouse (MLPKO) is a murine model of dilated cardiomyopathy (DCM) and HFrEF. The experimental timeline was to induce cRADΔ/Δ after onset of DCM (2.5 months of age) and follow subjects for up to 1-year. Longitudinal echocardiography and cardiac magnetic resonance imaging (CMR) showed that cRADΔ/Δ intervention rescued systolic function. Patch clamp recordings of isolated cardiomyocytes of MLPKO with cRADΔ/Δ demonstrated augmented LTCC activity, along with rescue of dysfunctional Ca2+ handling and sarcomere function. Bulk RNAseq of hearts demonstrated downregulated pathological signaling cascades and pro-hypertrophic gene expression which comported with the reduction in eccentric hypertrophy observed with gravimetrics, CMR, and echocardiography. RRAD knockdown effects translate from mouse to human heart. Ventricle slices from HFrEF patients were treated with lentiviral shRNA targeting RRAD and recapitulated the inotropic and lusitropic effects observed in the mouse model of DCM. Conclusions Induction of cardiomyocyte-restricted RAD knockout in MLPKO mice after onset of DCM rescued cardiac dysfunction and attenuated pathological remodeling. cRADΔ/Δ intervention provided positive inotropy and lusitropy and reverted transcriptional signatures towards healthy myocardium. This study introduces targeting myocardial RAD regulation of the LTCC as a novel therapeutic strategy for systolic heart failure.
2025-12-09 | GSE304830 | GEO
Project description:We developed a 5'RNA-seq methodology to concurrently assess gene expression and start-site usage changes. We applied this methodology to study hypertrophic cardiomyopathy in mice harboring a human deleterious mutation. 5'RNA-seq analysis of transcriptomes from mouse hearts with or without hypertrophic cardiomyopathy. Biological replicates were pooled into a single sequencing run. 5'RNA-seq methodology consists of enhanced sequencing of 5' ends and computational assessment of changes at start-sites of genes.
2013-11-05 | E-GEOD-52038 | biostudies-arrayexpress
Project description:Efficient correction of a hypertrophic cardiomyopathy mutation in mouse embryos by ABEmax-NG (Mouse)
| PRJNA728874 | ENA
Project description:Microarray profiling of STEP knockout mouse striatum
| PRJNA224547 | ENA
Project description:Importantly, mutations in nuclear envelope-encoding genes are the second-highest cause of familial dilated cardiomyopathy. One such nuclear envelope protein that causes cardiomyopathy in humans and affects mouse heart development is Lem2. However, its role in mechanically active tissue such as heart remains poorly understood.
2023-09-13 | GSE217693 | GEO
Project description:Beneficial Effects of High Intensity Interval Training in a Mouse Model of Hypertrophic Cardiomyopathy
| PRJNA1265749 | ENA
Project description:HipSci - Hypertrophic Cardiomyopathy - Exome Sequencing - July 2017
| EGAD00001003523 | EGA