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
| Autor: | David Ziupa, Heiko Bugger, Anna Ryan de Medeiros, Marius Menza, Corinna N. Lang, Stefanie Perez-Feliz, Jan C. Behrends, Michael Brunner, Naga Deepa Pantulu, Lea Mettke, Konstantin Michaelides, Zoltán Doleschall, Raphaela Rieke, Rémi Peyronnet, Geneviève Jolivet, Christoph Bode, Axel zur Hausen, Hannah E Fürniss, Ilona Bodi, Manfred Zehender, Katja E. Odening, Johannes Steinfurt, Gerlind Franke |
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| Přispěvatelé: | Department of Cardiology and Angiology I, University Heart Centre Freiburg - Bad Krozingen, University of Freiburg [Freiburg], Department of Pathology, University of Alabama at Birmingham [ Birmingham] (UAB), Department of Pathogenetics, National Institute of Oncology, Biologie du Développement et Reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Université Paris Saclay (COmUE), St. Josefskrankenhaus, German Research Foundation DFG-BR2107/4-1, MUMC+: DA Klinische Pathologie (5), Pathologie, RS: GROW - R2 - Basic and Translational Cancer Biology |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
Action Potentials 030204 cardiovascular system & hematology Ventricular tachycardia Animals Genetically Modified Electrocardiography 0302 clinical medicine MUTATION [SDV.BDD]Life Sciences [q-bio]/Development Biology biology Quinidine animal models Phenotype Ion channels Cardiology Female Rabbits medicine.symptom Cardiology and Cardiovascular Medicine Anti-Arrhythmia Agents medicine.drug Heart Defects Congenital medicine.medical_specialty Heart Ventricles hERG arrhythmia QT interval Sudden death 03 medical and health sciences SUDDEN-DEATH Heart Conduction System Internal medicine medicine Animals Humans Heart Atria Fibrillation business.industry Arrhythmias Cardiac Short QT syndrome 030229 sport sciences medicine.disease electrical remodelling Disease Models Animal Ventricular fibrillation biology.protein cardiac repolarization business short-QT syndrome |
| Zdroj: | European Heart Journal European Heart Journal, Oxford University Press (OUP): Policy B, 2019, 40 (10), pp.842-853. ⟨10.1093/eurheartj/ehy761⟩ European Heart Journal, 40(10), 842-853. Oxford University Press |
| ISSN: | 0195-668X 1522-9645 |
| DOI: | 10.1093/eurheartj/ehy761⟩ |
| Popis: | AIMS Short-QT syndrome 1 (SQT1) is an inherited channelopathy with accelerated repolarization due to gain-of-function in HERG/IKr. 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 β-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, 147.8 ± 2 ms vs. 166.4 ± 3, P |
| Databáze: | OpenAIRE |
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