Naturally occurring variation in cardiovascular traits among inbred mouse strains

The objective of this study was to characterize genetic variation in complex cardiovascular traits in two commonly used inbred mouse strains. We performed echocardiography, graded treadmill exercise, tail cuff plethysmography, and telemetry (heart rate, activity, temperature) in age- (similar to 9 weeks) and sex-matched A/J and C57BL/6J (136) inbred mice. B6 mice had significantly larger end-diastolic dimension (3.31 +/- 0.42 mm versus 2.83 +/- 0.31 mm) and left ventricle mass (46.2 +/- 14.1 versus 32.7 +/- 11.5 g) than A/J mice. This relative hypertrophy was eccentric (relative wall thickness ratios: 0.30 +/- 0.01 versus 0.32 +/- 0.01) and was not associated with a difference in systolic blood pressure (122.0 +/- 13.2 versus 123.1 +/- 20.8 mmHg). Left ventricle fractional shortening (39.1 +/- 6.2 versus 47.1 +/- 6.9%) and heart rate (433 55 versus 524 45 beats per minute) were significantly lower in 136 versus A/J respectively, resulting in similar resting echocardiographic cardiac indices (0.58 +/- 0.19 versus 0.50 +/- 0.17 ml/min/g). Maximum exercise time on a treadmill was significantly greater in 136 than in A/J mice (9.6 +/- 3.4 versus 4.4 +/- 1.9 minutes). Telemetry showed that body temperature was generally greater and heart rate lower in 136 than A/J; the relation with activity was more complex. These data suggest that relative to A/J, B6 mice have a phenotype characteristic of the "athlete's heart," that is, eccentric, physiologic hypertrophy, slower heart rates, and increased exercise endurance. This systematic characterization of functionally related cardiovascular traits in A/J and C57BL/6J mice revealed numerous differences whose genetic bases can be dissected with recombinant inbred, recombinant congenic, and chromosome substitution strains.