Key result
The R403Q mutation increased actin-activated ATPase by 38% and reduced b frequency by 27%, whereas R453C reduced ATPase by 45% and increased b frequency by 18% compared with wild-type mice.
Population
Heterozygous (R403Q/+ and R453C/+) male mouse hearts (isolated myosin and skinned strips)
Comparison
Cardiac myosin point mutations R403Q and R453C vs Wild-type (WT) mice
Design
Preclinical
Authors
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Differential kinetics in HCM mouse models leave open mutation-specific therapies; human validation required before clinical consideration.
The R403Q and R453C myosin mutations associated with familial hypertrophic cardiomyopathy exhibit markedly different cross-bridge kinetics and calcium sensitivity, suggesting distinct molecular pathomechanisms.
Palmer et al. (2004) studied Familial hypertrophic cardiomyopathy (FHC). Cardiac myosin point mutations R403Q and R453C vs. Wild-type (WT) mice was evaluated on Cross-bridge kinetic parameters and calcium sensitivity of force production. The R403Q mutation increased actin-activated ATPase by 38% and reduced b frequency by 27%, whereas R453C reduced ATPase by 45% and increased b frequency by 18% compared with wild-type mice.
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