DCM-Rat-TTNtv-2016
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB13824 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR1697210.fastq.gz | Fastqsanger.gz | |||
| ERR1697220.fastq.gz | Fastqsanger.gz | |||
| ERR1697230.fastq.gz | Fastqsanger.gz | |||
| ERR1699780_1.fastq.gz | Fastqsanger.gz | |||
| ERR1699780_2.fastq.gz | Fastqsanger.gz |
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Project description:Background: RBM20 gene is one of the genetic predispositions for dilated cardiomyopathy (DCM). Variants in RS domain has been reported in many DCM patients, while the pathogenicity of variants within the RNA-recognition motif remains unknown. Methods and results: We detected two human patients of I536T-RBM20 variant without DCM phenotype in sudden death cohorts. We performed splicing reporter assay and generated I538T knock-in (KI) mouse model (Rbm20I538T) in order to reveal the significance of this variant. The reporter assay revealed that human I536T variant affected TTN splicing pattern compared to wild-type. In the mouse experiments, Rbm20I538T mice presented a different splicing pattern in Ttn, Ldb3, Camk2d and Ryr2. The expression of Casq1, Mybpc2 and Myot were upregulated in Rbm20I538T mice. Whereas, Rbm20I538T mice did show neither DCM nor cardiac dysfunction by histopathological examination and ultrasound echocardiography. Conclusion: I536T-RBM20 (I538T-Rbm20) variant does not cause DCM phenotype, but changes the gene splicing and expression effect. The splicing and expression changes in Ttn and Ca handling genes such as Casq1, Camk2d and Ryr2 may be contributory to sudden arrhythmogenic death.
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Project description:Mutations in the sarcomeric protein titin are a major cause of human dilated cardiomyopathy. We have developed a knock-in mouse model that imitated a previously identified titin truncation mutation. The heterotygous Ttn-deficient mice develop features of DCM and therefore recapitulate the human phenotype. To investigate the role of microRNAs in titin-based heart failure, we performed a miRNA screen in heterozygous Ttn-deficient mice and their wildtype littermate controls.
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Project description:We wanted to see whether the set of affected genes in ischemic cardiomyopathy (ICM) is the same or different as compared to dilated cardiomyopathy (DCM). To find this out, we placed the single DCM sample on the same microarray slide with the ICM samples. Analysis of microarray data with ICM samples only showed 63 affected genes, while that carried out with 2 ICM samples PLUS one DCM sample reduced this number to just four genes. From this result we conclude that ICM and DCM affect different sets of genes in ventricular myocytes. Keywords: Expression profiling by array From the associated publication: To find out whether the splice microarray results reported in Table 3 are disease-type specific, we supplemented the same splice microarray of ICM ventricular myocytes with one additional sample prepared from left ventricle of a 41-years old dilated cardiomyopathy male donor. The top-list ANOVA gene score annotation for combined altered CE&P genes in ventricular myocytes (Table 3) was reduced from 63 to just 4 genes (FXYD1 (Gfold = +2.4), HCN2 (-1.5), GLRA1 (-1.8) and GJC1 (-2.3)).
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