Item type |
デフォルトアイテムタイプ(フル)(1) |
公開日 |
2021-04-27 |
タイトル |
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タイトル |
A missense mutation in the RSRSP stretch of Rbm20 causes dilated cardiomyopathy and atrial fibrillation in mice |
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言語 |
en |
作成者 |
Ihara, Kensuke
Sasano, Tetsuo
Hiraoka, Yuichi
Togo-Ohno, Marina
Soejima, Yurie
Sawabe, Motoji
Tsuchiya, Megumi
Ogawa, Hidesato
Furukawa, Tetsushi
Kuroyanagi, Hidehito
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アクセス権 |
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アクセス権 |
open access |
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アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
権利情報 |
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言語 |
en |
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権利情報 |
Creative Commons Attribution 4.0 |
権利情報 |
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言語 |
ja |
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権利情報 |
© The Author(s) 2020 |
権利情報 |
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言語 |
en |
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権利情報Resource |
https://creativecommons.org/licenses/by/4.0/ |
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権利情報 |
https://creativecommons.org/licenses/by/4.0/ |
内容記述 |
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内容記述タイプ |
Other |
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内容記述 |
Dilated cardiomyopathy (DCM) is a fatal heart disease characterized by left ventricular dilatation and cardiac dysfunction. Recent genetic studies on DCM have identified causative mutations in over 60 genes, including RBM20, which encodes a regulator of heart-specific splicing. DCM patients with RBM20 mutations have been reported to present with more severe cardiac phenotypes, including impaired cardiac function, atrial fibrillation (AF), and ventricular arrhythmias leading to sudden cardiac death, compared to those with mutations in the other genes. An RSRSP stretch of RBM20, a hotspot of missense mutations found in patients with idiopathic DCM, functions as a crucial part of its nuclear localization signals. However, the relationship between mutations in the RSRSP stretch and cardiac phenotypes has never been assessed in an animal model. Here, we show that Rbm20 mutant mice harboring a missense mutation S637A in the RSRSP stretch, mimicking that in a DCM patient, demonstrated severe cardiac dysfunction and spontaneous AF and ventricular arrhythmias mimicking the clinical state in patients. In contrast, Rbm20 mutant mice with frame-shifting deletion demonstrated less severe phenotypes, although loss of RBM20-dependent alternative splicing was indistinguishable. RBM20^<S637A> protein cannot be localized to the nuclear speckles, but accumulated in cytoplasmic, perinuclear granule-like structures in cardiomyocytes, which might contribute to the more severe cardiac phenotypes. |
内容記述 |
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内容記述タイプ |
Other |
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内容記述 |
論文 |
出版者 |
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言語 |
en |
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出版者 |
Springer Nature |
言語 |
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言語 |
eng |
資源タイプ |
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資源タイプ |
journal article |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
出版タイプ |
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出版タイプ |
VoR |
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出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
識別子 |
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識別子 |
http://hdl.handle.net/20.500.12000/48368 |
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識別子タイプ |
HDL |
関連情報 |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1038/s41598-020-74800-8 |
関連情報 |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1038/s41598-020-74800-8 |
収録物識別子 |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
2045-2322 |
収録物名 |
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言語 |
en |
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収録物名 |
Scientific Reports |
書誌情報 |
巻 10,
発行日 2020-10-27
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