Figure 3. DKO mice exhibit hypertrophic cardiomyopathy and decreased cardiac function.

(A) H&E stain of hearts. Solid and dotted lines indicate outer myofiber and inner core diameter, respectively. (B) Heart weight/body weight ratios showed cardiac hypertrophy in DKO mice. (C) Echocardiography revealed decreased LV systolic function (fractional shortening), increased LV end-systolic diameter (LVESD), and an unchanged LV end-diastolic diameter (LVEDD). (D) Electron microscopy of heart showed accumulated and disoriented thick filaments and displacement of mitochondria (arrow). Solid and dotted lines indicate outer myofiber and inner core diameter, respectively. Bottom panel is magnification the box in the top right panel, showing ultrastructure of accumulated myosin filaments in the cardiomyocyte. (E) Immunoblotting of proteins from hearts revealed accumulation of undegraded (cytosolic fraction; top 3 panels) and degraded (pellet fraction; bottom 2 panels) β/slow MHC in DKO muscle. α-MHC expression remained unchanged. (F) Expression of hypertrophic markers ANF and β/slow MHC as assessed by real-time PCR analysis. α-MHC expression remained unchanged. ^#P < 0.01 versus WT and MuRF1^–/–; *P < 0.01 versus MuRF3^–/–. Scale bars: 1 mm (A, top); 20 μm (A, bottom); 2 μm (D).