Figure 2. Vps34-deficient mice develop hypertrophic cardiomyopathy–like cardiomyopathy.

(A) Immunofluorescence analyses to detect (upper panels) Vps34 (green) and (middle panels) a phosphatidylinositol 3-phosphate bioprobe (GFP-EEA1-FYVE) in cardiac left ventricular sections from mice of the indicated genotypes. Representative images are shown. Blue, DAPI staining to detect nuclei. Arrowheads indicate GFP⁺ puncta. Scale bars: 10 μm. (Lower panels) GFP⁺ puncta were counted in 4 randomly chosen fields (10,000 μm²) for each sample (n = 4/group). **P < 0.01, 2-tailed Student’s t test. (B) Kaplan-Meier survival curves for mckCre-Vps34^fl/fl (cVps34^–/–) (n = 86), mckCre-Vps34^fl/+ (cVps34^+/–) (n = 61), and Vps34^fl/fl (cVps34^+/+) (n = 70) mice over the indicated period. All cVps34^–/– mice were dead by P110. ***P < 0.001, log-rank test. (C) Heart weight to body weight ratios for individual cVps34^+/+ (n = 40) and cVps34^–/– (n = 39) mice over the indicated period. Linear regression lines are shown. ***P < 0.001, Pearson’s test. (D) Macroscopic views of hearts from cVps34^+/+ and cVps34^–/– mice at the indicated ages. Results are representative of at least 10 hearts examined per group. P, postnatal day. (E) Representative M-mode echocardiograms of cVps34^+/+ and cVps34^–/– mice (n = 6/group) at P80. (F) Electrocardiograms at P80 showing short runs of premature ventricular contraction (arrows), QT elongation, and bundle branch block (right panels) in a cVps34^–/– mouse.