Fig. 1: Cardiomyocyte-specific loss of Kdm8 causes DCM leading to lethal heart failure.
From: KDM8 epigenetically controls cardiac metabolism to prevent initiation of dilated cardiomyopathy
a, Hearts from 2-month-old and 6-month-old Kdm8fl/fl control and Kdm8fl/fl;Myh6-Cre mutant mice. Scale bar, 1 mm. b, Heart weight normalized to the tibia length of control, heterozygous (Kdm8fl/+;Myh6-Cre), and mutant mice. Data are mean ± s.e.m. Two-way ANOVA with multiple comparison and Sidak correction. n = 27 control, 5 heterozygous, and 25 mutant 2-month-old mice per group. n = 21 control, 7 heterozygous, and 8 mutant 4-month-old mice. n = 8 control, 6 heterozygous, and 8 mutant 6-month-old mice. c, Representative sections of three hearts from 2-month-old and 6-month-old control and mutant mice, stained with Masson’s trichrome. RA, right atrium; LA, left atrium; RV, right ventricle; LV, left ventricle; IVS, interventricular septum. Scale bar, 1 mm. d, Thickness of the wall of the LV, RV, and IVS, and diameter of the LV at end-diastole (EDD) measured from sections of 6-month-old hearts. Data are mean ± s.e.m. Two-tailed Student’s t-test. n = 4 controls and 6 mutants. e, Immunofluorescence of Col5a1 and α-actinin on sections of 2-month-old and 6-month-old hearts. Nuclei were counterstained with 4′,6-diamidino-2-phenylindole (DAPI). Scale bar, 50 μm. Images are representative of three independent staining experiments. f, Area of Col5a1 signal in view field. Data are mean ± s.e.m. Two-tailed Student’s t-test. n = 3 mice per group. g, Echocardiogram of the LV of control and mutant mice. The blue line shows the diameter of the LV at end-systole. h, LV anterior wall (AW) thickness at end-systole. i, LV end-systolic diameter. j, LV end-diastolic diameter. k, LV ejection fraction. l, Isovolumetric relaxation time normalized to the time between heartbeats (IVRT/RR). Data in h to l are mean ± s.e.m. Two-way ANOVA with multiple comparison correction by Tukey’s method. n = 6–11 mice per group (see Source data for P values). m, Survival curve of control, Kdm8 heterozygous, and mutant mice analyzed by log-rank (Mantel–Cox) test. n = 10 control, 10 heterozygous, and 21 mutant mice.
