Extended Data Fig. 2: Exercise tolerance and cardiac function in female WT and KO mice after endurance training.

a, Treadmill exhaustion test results showing maximum velocity and distance run before exhaustion in 14-week-old female WT and KO mice pre- and post-training. b, Representative M-mode echocardiographic images at rest in WT and KO mice from (a) before and after 6 weeks of voluntary wheel running. c, Echocardiographic measurements in WT and KO mice from (a), including fractional shortening (FS), left ventricular internal diameter at diastole (LVIDd), interventricular septal thickness at diastole (IVSd), and left ventricular posterior wall thickness at diastole (LVPWd). d, Heart weight normalized to tibia length in sedentary vs exercise-trained WT and KO mice. Data are shown as mean ± s.e.m. For (a), (c), and (d), statistical significance was assessed by two-sided two-way ANOVA followed by Sidak’s multiple comparisons test. For a-b, n = 5 mice per group (WT and KO pre-training), and n = 4 mice per group (WT and KO post-training). For (c), n = 4 mice/group. All data points represent individual mice as biological replicates. For echocardiographic quantifications in (c), single measurements were made per mouse. Exact P values: a, Max treadmill velocity: 0.95 (pre), 0.000072 (post); a, Max distance: 0.94 (pre), 0.00041 (post); c, FS: 0.42 (pre), 8.1e-9 (post); c, LVIDd: 0.78 (pre), 6.8e-8 (post); c, IVSd: 0.16 (pre), 0.000028 (post); c, LVPWd: 1.0 (pre), 0.00070 (post); d, Heart weight/tibia length: 0.31 (sedentary), 0.00068 (trained). Significance symbols: *P < 0.05, **P < 0.01, **P < 0.001; N.S., not significant. For all data in this figure, a single experiment was performed without a separate biological replication cohort. Mouse strain and age: all data in this experiment was derived from 14 week old female mice (age relative to initiation of the experiment) of the indicated strains (WT vs. KO as defined above) and n per group.

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