Comparison of the effects of a truncating and a missense MYBPC3 mutation on contractile parameters of engineered heart tissue
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- 作者：Paul J.M. Wijnkera ; b ; c ; Felix W. Friedricha ; b ; Alexander Dutscha ; b ; Silke Reischmanna ; b ; Alexandra Edera ; b ; Ingra Mannhardta ; b ; Giulia Mearinia ; b ; Thomas Eschenhagena ; b ; Jolanda van der Veldenc ; Lucie Carriera ; b ; l.carrier@uke.de" class="auth_mail" title="E-mail the corresponding author
- 关键词：Cardiac myosin-binding protein-C ; Engineered heart tissue ; Haploinsufficiency ; Hypertrophic cardiomyopathy ; Missense mutation ; Truncating mutation
- 刊名：Journal of Molecular and Cellular Cardiology
- 出版年：2016
- 出版时间：August 2016
- 年：2016
- 卷：97
- 期：Complete
- 页码：82-92
- 全文大小：1250 K
文摘
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MYBPC3, encoding cardiac myosin-binding protein-C is the most frequently mutated gene in hypertrophic cardiomyopathy (HCM).
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A truncating and a missense MYBPC3 mutation were expressed in engineered heart tissue (EHT) from Mybpc3-KO mice.
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KO EHTs displayed higher maximal force and sensitivity to external [Ca2+] than WT EHTs.
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Haploinsufficiency affected EHT contractile function if WT cMyBP-C protein levels were ≤ 73%.
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Missense or truncating mutation, but not WT did not fully restore the disease phenotype and had different pathogenic mechanisms, e.g. sarcomere poisoning for the missense mutation in KO EHTs.