論文

査読有り
2014年8月

Transgenic expression of the N525S-tuberin variant in Tsc2 mutant (Eker) rats causes dominant embryonic lethality

SCIENTIFIC REPORTS
  • Masatoshi Shiono
  • ,
  • Toshiyuki Kobayashi
  • ,
  • Riichi Takahashi
  • ,
  • Masatsugu Ueda
  • ,
  • Chikashi Ishioka
  • ,
  • Okio Hino

4
開始ページ
5927
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/srep05927
出版者・発行元
NATURE PUBLISHING GROUP

The Tsc2 product, tuberin, negatively regulates the mTOR pathway. We have exploited the Eker (Tsc2-mutant) rat system to analyse various Tsc2 mutations. Here, we focus on the N525S-Tsc2 variant (NSM), which is known to cause distinct symptoms in patients even though normal suppression of mTOR is observed. Unexpectedly, we were repeatedly unable to generate viable rats carrying the NSM transgene. Genotypic analysis revealed that most of the embryos carrying the transgene died around embryonic day after 14.5-similar to the stage of lethality observed for Eker homozygotes. Thus, the NSM transgene appeared to have a dominant lethal effect in our rat model. Further, no significant differences were observed for various signal transduction molecules in transiently expressed NSM cells compared to WT. These results indicate that a non-mTOR pathway, critical for embryogenesis, is being regulated by tuberin, providing a link between tuberin expression and the severity of Tsc2 mutation-related pathogenesis.

Web of Science ® 被引用回数 : 1

リンク情報
DOI
https://doi.org/10.1038/srep05927
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/25088526
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000339941400001&DestApp=WOS_CPL