論文

査読有り
2013年6月

Mouse Otocyst Transuterine Gene Transfer Restores Hearing in Mice With Connexin 30 Deletion-associated Hearing Loss

MOLECULAR THERAPY
  • Toru Miwa
  • ,
  • Ryosei Minoda
  • ,
  • Momoko Ise
  • ,
  • Takao Yamada
  • ,
  • Eiji Yumoto

21
6
開始ページ
1142
終了ページ
1150
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/mt.2013.62
出版者・発行元
NATURE PUBLISHING GROUP

Although numerous causative genes for hereditary hearing loss have been identified, there are no fundamental treatments for this condition. Herein, we describe a novel potential treatment for genetic hearing loss. Because mutations or deletions in the connexin (Cx) genes are common causes of profound congenital hearing loss in both humans and mice, we investigated whether gene supplementation therapy using the wild-type Cx gene could cure hearing loss. We first generated inner ear-specific connexin 30 (Cx30)-deficient mice via the transuterine transfer of Cx30-targeted short hairpin RNA (shRNA-Cx30) into otocysts. The inner ear-specific Cx30-deficient mice mimicked homozygous Cx30-deficient mice both histologically and physiologically. Subsequently, we cotransfected the shRNA-Cx30 and the wild-type Cx30 gene. The cotransfected mice exhibited Cx30 expression in the cochleae and displayed normal auditory functions. Next, we performed the transuterine transfer of the wild-type Cx30 gene into the otocysts of homozygous Cx30-deficient mice, thereby rescuing the lack of Cx30 expression in the cochleae and restoring auditory functioning. These results demonstrate that supplementation therapy with wild-type genes can restore postnatal auditory functioning. Moreover, this is the first report to show that Cx-related genetic hearing loss is treatable by in vivo gene therapy.

Web of Science ® 被引用回数 : 31

リンク情報
DOI
https://doi.org/10.1038/mt.2013.62
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/23587925
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000319859000008&DestApp=WOS_CPL

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