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Transduction of full-length dystrophin to multiple skeletal muscles improves motor performance and life span in utrophin/dystrophin double knockout mice
http://hdl.handle.net/2298/10918
http://hdl.handle.net/2298/10918effc27fe-ed23-4e94-8be0-d1f8a3800e04
名前 / ファイル | ライセンス | アクション |
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Mol Ther_016_825.pdf (302.3 kB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2009-02-23 | |||||
タイトル | ||||||
タイトル | Transduction of full-length dystrophin to multiple skeletal muscles improves motor performance and life span in utrophin/dystrophin double knockout mice | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題 | dystrophin, Duchenne muscular dystrophy, DMD | |||||
資源タイプ | ||||||
資源タイプ | journal article | |||||
著者 |
Kawano, Ryoko
× Kawano, Ryoko× Ishizaki, Masatoshi× Maeda, Yasushi× Uchida, Yuji× 木村, 円× Uchino, Makoto |
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別言語の著者 |
河野, 亮子
× 河野, 亮子× 石崎, 雅俊× 前田, 寧× 内田, 友二× 木村, 円× 内野, 誠 |
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内容記述 | ||||||
内容記述 | Duchenne muscular dystrophy (DMD) is a fatal, progressive, muscle-wasting disease caused by defects in the dystrophin. No viral vector except the helper-dependent adenovirus vector (HDAdv) can package 14-kilobase (kb) full-length dystrophin complementary DNA (cDNA), and HDAdv is considerably safer than old-generation adenovirus vectors because of the large-size deletion in its genome. We have generated HDAdv that carries myc-tagged murine full-length dystrophin cDNA (HDAdv-myc-mFLdys). We injected it into multiple proximal muscles of 7-day-old utrophin/dystrophin double knockout mice (dko mice) (which typically show symptoms quite similar to human DMD) because the proximal muscles are affected in DMD patients. Eight weeks after the injections, the transduced dystrophin was widely expressed, and we found a significant reduction in centrally nucleated myofibers and the restoration of the dystrophin-associated proteins, β-dystroglycan (β-DG) and α-sarcoglycan (α-SG), as well as neuronal nitric oxide synthase (nNOS). The injected dko mice also showed an increase in body weight, an improvement in motor performance, and a prolongation of life span. Using HDAdv, we could treat DMD model mice even by transferring the therapeutic gene into multiple skeletal muscles. Our results suggest that multiple intramuscular administrations of HDAdv carrying full-length dystrophin cDNA may reduce symptoms and compensate for lost functions in DMD patients. | |||||
書誌情報 |
Molecular Therapy 巻 16, 号 5, p. 825-831, 発行年 2008-05 |
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書誌レコードID | ||||||
収録物識別子 | AA11475060 | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
関連識別子 | 10.1038/mt.2008.23 | |||||
権利 | ||||||
権利情報 | © 2008 American Society of Gene Therapy | |||||
情報源(ISSN) | ||||||
関連名称 | 15250016 | |||||
フォーマット | ||||||
内容記述 | application/pdf | |||||
形態 | ||||||
302252 bytes | ||||||
著者版フラグ | ||||||
出版タイプ | AM | |||||
日本十進分類法 | ||||||
主題 | 493.6 | |||||
出版者 | ||||||
出版者 | Nature Publishing Group | |||||
資源タイプ | ||||||
内容記述 | 論文(Article) | |||||
資源タイプ・ローカル | ||||||
雑誌掲載論文 | ||||||
資源タイプ・NII | ||||||
Journal Article | ||||||
資源タイプ・DCMI | ||||||
text | ||||||
資源タイプ・ローカル表示コード | ||||||
01 | ||||||
部分である | ||||||
関連タイプ | isPartOf | |||||
関連識別子 | http://hdl.handle.net/2298/9668 | |||||
URL | ||||||
内容記述 | http://www.nature.com/mt/journal/v16/n5/abs/mt200823a.html | |||||
コメント | ||||||
平成18~19年度科学研究費補助金(基盤研究(C)(2))研究成果報告書 課題番号:18590951 新世代アデノウイルスベクターとトランスポゼースによる進行性筋ジストロフィーの遺伝子治療 に掲載 |