Transgenic short-QT syndrome 1 rabbits mimic the human disease phenotype with QT/action potential duration shortening in the atria and ventricles and increased ventricular tachycardia/ventricular fibrillation inducibility

Katja E. Odening*, Ilona Bodi, Gerlind Franke, Raphaela Rieke, Anna Ryan de Medeiros, Stefanie Perez-Feliz, Hannah Fuerniss, Lea Mettke, Konstantin Michaelides, Corinna N. Lang, Johannes Steinfurt, Naga Deepa Pantulu, David Ziupa, Marius Menza, Manfred Zehender, Heiko Bugger, Remi Peyronnet, Jan C. Behrends, Zoltan Doleschall, Axel Zur HausenChristoph Bode, Genevieve Jolivet, Michael Brunner

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Aims Short-QT syndrome 1 (SQT1) is an inherited channelopathy with accelerated repolarization due to gain-of-function in HERG/I-Kr. Patients develop atrial fibrillation, ventricular tachycardia (VT), and sudden cardiac death with pronounced inter-individual variability in phenotype. We generated and characterized transgenic SQT1 rabbits and investigated electrical remodelling.

Methods and results Transgenic rabbits were generated by oocyte-microinjection of -myosin-heavy-chain-promoter-KCNH2/HERG-N588K constructs. Short-QT syndrome 1 and wild type (WT) littermates were subjected to in vivo ECG, electrophysiological studies, magnetic resonance imaging, and ex vivo action potential (AP) measurements. Electrical remodelling was assessed using patch clamp, real-time PCR, and western blot. We generated three SQT1 founders. QT interval was shorter and QT/RR slope was shallower in SQT1 than in WT (QT, 147.82ms vs. 166.4 +/- 3, P

Conclusion Short-QT syndrome 1 rabbits mimic the human disease phenotype on all levels with shortened QT/APD and increased VT/VF-inducibility and show similar beneficial responses to quinidine, indicating their value for elucidation of arrhythmogenic mechanisms and identification of novel anti-arrhythmic strategies.

Original languageEnglish
Pages (from-to)842-853
Number of pages12
JournalEuropean Heart Journal
Issue number10
Publication statusPublished - 7 Mar 2019


  • Short-QT syndrome
  • Animal models
  • Cardiac repolarization
  • Ion channels
  • Electrical remodelling
  • Arrhythmia

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