Key result
The R403Q mutation enhanced the ADP release rate by 20% (to 430 s−1) in mouse α-cardiac myosin but caused only a minor reduction in kinetics for β-cardiac myosin.
Population
Transgenic mouse model in which endogenous α-MHC was partially replaced with transgenically encoded β-MHC or…
Comparison
R403Q mutation in α-S1 and β-S1 cardiac myosin… vs Wild-type α-S1 and β-S1 cardiac myosin isoforms
Design
Preclinical
Authors
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Isoform-dependent R403Q effects caution against α-MHC mouse models for human β-MHC HCM; leaves open need for matched isoform studies.
The functional impact of the R403Q mutation on cardiac myosin kinetics depends on the isoform backbone, indicating that mouse models expressing α-MHC may not fully recapitulate the human hypertrophic cardiomyopathy phenotype driven by β-MHC.
Lowey et al. (2013) studied Familial hypertrophic cardiomyopathy. R403Q mutation in α- and β-cardiac myosin heavy chain vs. Wild-type isoforms was evaluated on Equilibrium constants and rates of nucleotide binding and release. The R403Q mutation enhanced the ADP release rate by 20% (to 430 s−1) in mouse α-cardiac myosin but caused only a minor reduction in kinetics for β-cardiac myosin.
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