The embryological basis of subclinical hypertrophic cardiomyopathy
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The embryological basis of subclinical hypertrophic cardiomyopathy. / Captur, Gabriela; Ho, Carolyn Y; Schlossarek, Saskia; Kerwin, Janet; Mirabel, Mariana; Wilson, Robert; Rosmini, Stefania; Obianyo, Chinwe; Reant, Patricia; Basset, Paul; Cook, Andrew C; Lindsay, Susan; McKenna, William; Mills, Kevin; Elliott, Perry M; Mohun, Timothy J; Carrier, Lucie; Moon, James C.
In: SCI REP-UK, Vol. 6, 2016, p. 27714.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - The embryological basis of subclinical hypertrophic cardiomyopathy
AU - Captur, Gabriela
AU - Ho, Carolyn Y
AU - Schlossarek, Saskia
AU - Kerwin, Janet
AU - Mirabel, Mariana
AU - Wilson, Robert
AU - Rosmini, Stefania
AU - Obianyo, Chinwe
AU - Reant, Patricia
AU - Basset, Paul
AU - Cook, Andrew C
AU - Lindsay, Susan
AU - McKenna, William
AU - Mills, Kevin
AU - Elliott, Perry M
AU - Mohun, Timothy J
AU - Carrier, Lucie
AU - Moon, James C
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
U2 - 10.1038/srep27714
DO - 10.1038/srep27714
M3 - SCORING: Journal article
VL - 6
SP - 27714
JO - SCI REP-UK
JF - SCI REP-UK
SN - 2045-2322
ER -
