首页    期刊浏览 2024年11月30日 星期六
登录注册

文章基本信息

  • 标题:Loss of muscleblind-like 1 results in cardiac pathology and persistence of embryonic splice isoforms
  • 本地全文:下载
  • 作者:Donald M. Dixon ; Jongkyu Choi ; Ayea El-Ghazali
  • 期刊名称:Scientific Reports
  • 电子版ISSN:2045-2322
  • 出版年度:2015
  • 卷号:5
  • 期号:1
  • DOI:10.1038/srep09042
  • 语种:English
  • 出版社:Springer Nature
  • 摘要:Cardiac dysfunction is a prominent cause of mortality in myotonic dystrophy I (DM1), a disease where expanded CUG repeats bind and disable the muscleblind-like family of splice regulators. Deletion of muscleblind-like 1 ( Mbnl1ΔE2/ΔE2 ) in 129 sv mice results in QRS, QTc widening, bundle block and STc narrowing at 2–4 months of age. With time, cardiac function deteriorates further and at 6 months, decreased R wave amplitudes, sinus node dysfunction, cardiac hypertrophy, interstitial fibrosis, multi-focal myocardial fiber death and calcification manifest. Sudden death, where no end point illness is overt, is observed at a median age of 6.5 and 4.8 months in ~67% and ~86% of male and female Mbnl1ΔE2/ΔE2 mice, respectively. Mbnl1 depletion results in the persistence of embryonic splice isoforms in a network of cardiac RNAs, some of which have been previously implicated in DM1, regulating sodium and calcium currents, Scn5a , Junctin , Junctate , Atp2a1 , Atp11a , Cacna1s , Ryr2 , intra and inter cellular transport, Clta , Stx2 , Tjp1 , cell survival, Capn3 , Sirt2 , Csda , sarcomere and cytoskeleton organization and function, Trim55 , Mapt , Pdlim3 , Pdlim5 , Sorbs1 , Sorbs2 , Fhod1 , Spag9 and structural components of the sarcomere, Myom1 , Tnnt2 , Zasp . Thus this study supports a key role for Mbnl1 loss in the initiation of DM1 cardiac disease.
国家哲学社会科学文献中心版权所有