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Lookup NU author(s): Dr Janet KerwinORCiD, Emerita Professor Susan Lindsay
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Hypertrophic cardiomyopathy (HCM) is caused by mutations in sarcomeric proteins, the commonest being MYBPC3 encoding myosin-binding protein C. It is characterised by left ventricular hypertrophy but there is an important pre-hypertrophic phenotype with features including crypts, abnormal mitral leaflets and trabeculae. We investigated these during mouse cardiac development using high-resolution episcopic microscopy. In embryonic hearts from wildtype, homozygous (HO) and heterozygous (HET) Mybpc3-targeted knock-out (KO) mice we show that crypts (one or two) are a normal part of wildtype development but they almost all resolve by birth. By contrast, HO and HET embryos had increased crypt presence, abnormal mitral valve formation and alterations in the compaction process. In scarce normal human embryos, crypts were sometimes present. This study shows that features of the human pre-hypertrophic HCM phenotype occur in the mouse. In an animal model we demonstrate that there is an embryological HCM phenotype. Crypts are a normal part of cardiac development but, along with the mitral valve and trabeculae, their developmental trajectory is altered by the presence of HCM truncating Mybpc3 gene mutation.
Author(s): Captur G, Ho CY, Schlossarek S, Kerwin J, Mirabel M, Wilson R, Rosmini S, Obianyo C, Reant P, Bassett P, Cook AC, Lindsay S, McKenna WJ, Mills K, Elliott PM, Mohun TJ, Carrier L, Moon JC
Publication type: Article
Publication status: Published
Journal: Scientific Reports
Year: 2016
Volume: 6
Online publication date: 21/06/2016
Acceptance date: 24/05/2016
Date deposited: 18/08/2016
ISSN (electronic): 2045-2322
Publisher: Nature Publishing Group
URL: http://dx.doi.org/10.1038/srep27714
DOI: 10.1038/srep27714
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