Fig. 5: Overexpression of KLF15 prevents cardiac defects in Mrps5 mutant mice.
From: A defect in mitochondrial protein translation influences mitonuclear communication in the heart
a Experimental procedure to test the function of Klf15 in preventing the development of cardiomyopathy in Mrps5cKO mice. Neonatal Mrps5cKO mice were injected with control AAV9-Luci or AAV9-Klf15. Tamoxifen was injected at 4 weeks to induce the deletion of Mrps5 in the heart. Echocardiography was performed at indicated time points (M-mode data shown). b Gene expression of Klf15 in Mrps5cKO mice injected with AAV-Luci/Klf15, respectively. c–f Ejection fraction (EF), fractional shortening (FS), left ventricular systolic diameter (LVID;s), and left ventricular volume (LV Vol;s) were recorded in AAV9-Luci or AAV9-Klf15 injected Mrps5cKO mice at indicated time points. g Immunohistology of heart sections of Mrps5cKO mice after neonatal injection of AAV9-Luci or AAV9-Klf15. DAPI (nucleus), WGA (cell membrane), and ACTN1 (cardiomyocytes). Scale bars = 20 µm. h Quantification of cardiomyocyte size from Fig. 5g. i Heart weight to body weight ratio of AAV9-Luci or AAV9-Klf15 injected Mrps5cKO mice. j–m qRT-PCR analysis of Nppa, Nppb, Acta1, and Mrps5 genes in 19-week-old Mrps5cKO hearts after neonatal injection of AAV9-Luci or AAV9-Klf15. n Sirius Red and Fast Green staining of heart sections from Mrps5cKO mice at 19 weeks of age following neonatal injection of AAV9-Luci or AAV9-Klf15. Scale bars = 50 µm. o Quantification of fibrosis from hearts described in Fig. 5n. p TEM images of heart tissue from 19-week-old Mrps5cKO mice injected at the neonatal stage with AAV9-Luci or AAV9-Klf15. Scale bars as indicated. q Quantification of mitochondrial cristae length from hearts of mice described in Fig. 5p. r Quantification of mitochondrial numbers per µm2 in heart tissue from mice described in Fig. 5p. s Quantification of the mitochondrial area in heart tissue from mice described in Fig. 5p. h–o, q–s Comparisons between Mrps5cKO mice injected with AAV9-Luci (green) or AAV9-Klf15 (red), as indicated in the legend for (Fig. 5r). N numbers are indicated in each panel. All data were presented as mean ± SEM. P values were determined by a two-tailed unpaired Students’ t-test.
