Matches in SemOpenAlex for { <https://semopenalex.org/work/W4387637954> ?p ?o ?g. }
- W4387637954 abstract "Hypertrophic cardiomyopathy (HCM) is frequently caused by mutations in the cardiac myosin binding protein-C (cMyBP-C) encoding gene MYBPC3. In the Netherlands, approximately 25% of patients carry the MYBPC3c.2373InsG founder mutation. Most patients are heterozygous (MYBPC3+/InsG) and have highly variable phenotypic expression, whereas homozygous (MYBPC3InsG/InsG) patients have severe HCM at a young age. To improve understanding of disease progression and genotype-phenotype relationship based on the hallmarks of human HCM, we characterized mice with CRISPR/Cas9-induced heterozygous and homozygous mutations. At 18-28 weeks of age, we assessed the cardiac phenotype of Mybpc3+/InsG and Mybpc3InsG/InsG mice with echocardiography, and performed histological analyses. Cytoskeletal proteins and cardiomyocyte contractility of 3-4 week old and 18-28 week old Mybpc3c.2373InsG mice were compared to wild-type (WT) mice. Expectedly, knock-in of Mybpc3c.2373InsG resulted in the absence of cMyBP-C and our 18-28 week old homozygous Mybpc3c.2373InsG model developed cardiac hypertrophy and severe left ventricular systolic and diastolic dysfunction, whereas HCM was not evident in Mybpc3+/InsG mice. Mybpc3InsG/InsG cardiomyocytes also presented with slowed contraction-relaxation kinetics, to a greater extent in 18-28 week old mice, partially due to increased levels of detyrosinated tubulin and desmin, and reduced cardiac troponin I (cTnI) phosphorylation. Impaired cardiomyocyte contraction-relaxation kinetics were successfully normalized in 18-28 week old Mybpc3InsG/InsG cardiomyocytes by combining detyrosination inhibitor parthenolide and β-adrenergic receptor agonist isoproterenol. Both the 3-4 week old and 18-28 week old Mybpc3InsG/InsG models recapitulate HCM, with a severe phenotype present in the 18-28 week old model." @default.
- W4387637954 created "2023-10-15" @default.
- W4387637954 creator A5001481959 @default.
- W4387637954 creator A5006203141 @default.
- W4387637954 creator A5008468085 @default.
- W4387637954 creator A5017256014 @default.
- W4387637954 creator A5024874361 @default.
- W4387637954 creator A5059130593 @default.
- W4387637954 creator A5061049981 @default.
- W4387637954 creator A5069429076 @default.
- W4387637954 creator A5071583041 @default.
- W4387637954 creator A5077350547 @default.
- W4387637954 date "2023-10-01" @default.
- W4387637954 modified "2023-10-18" @default.
- W4387637954 title "Characterization of heterozygous and homozygous mouse models with the most common hypertrophic cardiomyopathy mutation MYBPC3 in the Netherlands" @default.
- W4387637954 cites W1976499329 @default.
- W4387637954 cites W1987736934 @default.
- W4387637954 cites W1991410616 @default.
- W4387637954 cites W1994999442 @default.
- W4387637954 cites W2006660609 @default.
- W4387637954 cites W2014534876 @default.
- W4387637954 cites W2040002009 @default.
- W4387637954 cites W2057459836 @default.
- W4387637954 cites W2061635752 @default.
- W4387637954 cites W2070536183 @default.
- W4387637954 cites W2085265044 @default.
- W4387637954 cites W2088510916 @default.
- W4387637954 cites W2092771760 @default.
- W4387637954 cites W2096087960 @default.
- W4387637954 cites W2100651399 @default.
- W4387637954 cites W2102903858 @default.
- W4387637954 cites W2103968029 @default.
- W4387637954 cites W2108872949 @default.
- W4387637954 cites W2114663889 @default.
- W4387637954 cites W2118379808 @default.
- W4387637954 cites W2121229923 @default.
- W4387637954 cites W2123486104 @default.
- W4387637954 cites W2125330691 @default.
- W4387637954 cites W2129357784 @default.
- W4387637954 cites W2139645827 @default.
- W4387637954 cites W2141307759 @default.
- W4387637954 cites W2146130130 @default.
- W4387637954 cites W2147922516 @default.
- W4387637954 cites W2150788617 @default.
- W4387637954 cites W2151433089 @default.
- W4387637954 cites W2151574637 @default.
- W4387637954 cites W2154605694 @default.
- W4387637954 cites W2155210048 @default.
- W4387637954 cites W2159669366 @default.
- W4387637954 cites W2273081455 @default.
- W4387637954 cites W2284855986 @default.
- W4387637954 cites W2336853363 @default.
- W4387637954 cites W2548238550 @default.
- W4387637954 cites W2565014548 @default.
- W4387637954 cites W2587480104 @default.
- W4387637954 cites W2626378188 @default.
- W4387637954 cites W2754442483 @default.
- W4387637954 cites W2756203218 @default.
- W4387637954 cites W2898270629 @default.
- W4387637954 cites W2899182703 @default.
- W4387637954 cites W2950652067 @default.
- W4387637954 cites W3000347972 @default.
- W4387637954 cites W3020456299 @default.
- W4387637954 cites W3043028179 @default.
- W4387637954 cites W3047545610 @default.
- W4387637954 cites W3088010440 @default.
- W4387637954 cites W3109175419 @default.
- W4387637954 cites W3121093645 @default.
- W4387637954 cites W3137486125 @default.
- W4387637954 cites W4206918415 @default.
- W4387637954 cites W4285500649 @default.
- W4387637954 cites W4386261551 @default.
- W4387637954 doi "https://doi.org/10.1016/j.yjmcc.2023.10.008" @default.
- W4387637954 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37844837" @default.
- W4387637954 hasPublicationYear "2023" @default.
- W4387637954 type Work @default.
- W4387637954 citedByCount "0" @default.
- W4387637954 crossrefType "journal-article" @default.
- W4387637954 hasAuthorship W4387637954A5001481959 @default.
- W4387637954 hasAuthorship W4387637954A5006203141 @default.
- W4387637954 hasAuthorship W4387637954A5008468085 @default.
- W4387637954 hasAuthorship W4387637954A5017256014 @default.
- W4387637954 hasAuthorship W4387637954A5024874361 @default.
- W4387637954 hasAuthorship W4387637954A5059130593 @default.
- W4387637954 hasAuthorship W4387637954A5061049981 @default.
- W4387637954 hasAuthorship W4387637954A5069429076 @default.
- W4387637954 hasAuthorship W4387637954A5071583041 @default.
- W4387637954 hasAuthorship W4387637954A5077350547 @default.
- W4387637954 hasBestOaLocation W43876379541 @default.
- W4387637954 hasConcept C104317684 @default.
- W4387637954 hasConcept C115725540 @default.
- W4387637954 hasConcept C126322002 @default.
- W4387637954 hasConcept C127716648 @default.
- W4387637954 hasConcept C134018914 @default.
- W4387637954 hasConcept C147447768 @default.
- W4387637954 hasConcept C174054327 @default.
- W4387637954 hasConcept C204232928 @default.
- W4387637954 hasConcept C207200792 @default.
- W4387637954 hasConcept C2778198053 @default.
- W4387637954 hasConcept C2778797674 @default.