Cardiomyocyte-specific EGFR downregulation acutely decreases cardiac function. (A) EGFR protein expression in adult EGFRf/f (Cre−) vs. CM-EGFR-KD left ventricular (LV) membrane samples normalized to α-catenin. ***P < 0.001, two-tailed unpaired t-test, n = 8 each. Ejection fraction (%EF, B) and fractional shortening (%FS, C) of EGFRf/f (Cre−) (n = 12), αMHC-Cre+ (n = 8) and CM-EGFR-KD (n = 11) mice were monitored via echocardiography from 6 to 13 weeks of age. *P < 0.05, ***P < 0.001 vs. EGFRf/f (Cre−), ordinary two-way ANOVA with Bonferroni’s multiple comparisons test. (D) EGFR protein expression in the hearts of adult EGFRf/f (Cre−) mice 4 weeks after treatment with AAV9-GFP vs. AAV9-Cre (top panels, n = 4 each) or in the hearts of adult CM-EGFR-KD mice 4 weeks after treatment with AAV9-lacZ vs. AAV9-EGFR (bottom panels, n = 6 each). *P < 0.05, two-tailed unpaired t-test. %EF (E) and %FS (F) of adult EGFRf/f (Cre−) mice treated with AAV9-GFP (n = 5) vs. AAV9-Cre (n = 6) or adult CM-EGFR-KD mice treated with AAV9-lacZ (n = 10) vs. AAV9-EGFR (n = 10) were monitored via echocardiography for 4 weeks following AAV administration (at time 0). ***P < 0.001 AAV9-EGFR vs. AAV9-LacZ in CM-EGFR-KD mice and †P < 0.05, †††P < 0.001 AAV9-Cre vs. AAV9-GFP in EGFRf/f (Cre−) mice at corresponding timepoints, ordinary two-way ANOVA with Bonferroni’s multiple comparisons test.