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タイトル: | Somatic chromosomal translocation between 𝘌𝘸𝘴𝘳1 and 𝘍𝘭𝘪1 loci leads to dilated cardiomyopathy in a mouse model |
著者: | Tanaka, Miwa Yamaguchi, Shuichi Yamazaki, Yukari Kinoshita, Hideyuki Kuwahara, Koichiro Nakao, Kazuwa Jay, Patrick Y. Noda, Tetsuo Nakamura, Takuro |
著者名の別形: | 木下, 秀之 中尾, 一和 |
キーワード: | Cardiomyopathies Cytogenetics DNA recombination Gene regulation |
発行日: | 2015 |
出版者: | Nature Publishing Group |
誌名: | Scientific Reports |
巻: | 5 |
論文番号: | 7826 |
抄録: | A mouse model that recapitulates the human Ewing's sarcoma-specific chromosomal translocation was generated utilizing the 𝘊𝘳𝘦/𝘭𝘰𝘹P-mediated recombination technique. A cross between 𝘌𝘸𝘴𝘳1-𝘭𝘰𝘹P and 𝘍𝘭𝘪1-𝘭𝘰𝘹P mice and expression of ubiquitous Cre recombinase induced a specific translocation between 𝘌𝘸𝘴𝘳1 and 𝘍𝘭𝘪1 loci in systemic organs of both adult mice and embryos. As a result 𝘌𝘸𝘴𝘳1-𝘍𝘭𝘪1 fusion transcripts were expressed, suggesting a functional 𝘌𝘸𝘴-𝘍𝘭𝘪1 protein might be synthesized in vivo. However, by two years of age, none of the 𝘌𝘸𝘴𝘳1-loxP/𝘍𝘭𝘪1-loxP/CAG-Cre (EFCC) mice developed any malignancies, including Ewing-like small round cell sarcoma. Unexpectedly, all the EFCC mice suffered from dilated cardiomyopathy and died of chronic cardiac failure. Genetic recombination between 𝘌𝘸𝘴𝘳1 and 𝘍𝘭𝘪1 was confirmed in the myocardial tissue and apoptotic cell death of cardiac myocytes was observed at significantly higher frequency in EFCC mice. Moreover, expression of 𝘌𝘸𝘴-𝘍𝘭𝘪1 in the cultured cardiac myocytes induced apoptosis. Collectively, these results indicated that ectopic expression of the 𝘌𝘸𝘴-𝘍𝘭𝘪1 oncogene stimulated apoptotic signals and suggested an important relationship between oncogenic signals and cellular context in the cell-of-origin of Ewing's sarcoma. |
著作権等: | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ |
URI: | http://hdl.handle.net/2433/293719 |
DOI(出版社版): | 10.1038/srep07826 |
PubMed ID: | 25591392 |
関連リンク: | http://api.elsevier.com/content/abstract/scopus_id/84954288461 |
出現コレクション: | 学術雑誌掲載論文等 |

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