FARS2 deficiency causes cardiac hypertrophy leading to heart failure and sudden death in vivo. A, Schematic diagram to generate 4-OH tamoxifen inducible cardiac-specific Fars2 knockout (icKO) mice by crossing Fars2LoxP/LoxP mice with Myh6-MerCreMer+ mice. B, Western blot analysis of FARS2 (mitochondrial phenylalanyl-tRNA synthetase) protein levels in the heart and liver of wild-type (WT) control and FARS2 icKO mice, with GAPDH as loading control. C, Photograph of WT and icKO male mice at 12 weeks after icKO. D, Kaplan-Meier survival curves for WT and icKO mice (n=16–19). The median survival times for the icKO group are marked. E, Ratios of heart weight to tibia length (HW/TL; n=3–16). F, Relative mRNA levels of cardiac hypertrophy markers (Nppa, Nppb, and Myh7) in mice 3, 10, and 12 weeks after icKO (n=3). G, Representative heart (scale bar=2 mm), longitudinal sections (scale bar=2 mm), Masson trichrome staining (scale bar=25 μm), hematoxylin & eosin staining (scale bar=25 μm), and wheat germ agglutinin staining (scale bar=25 μm) from male mice at 3, 10, and 12 weeks after icKO and WT (10 weeks after icKO). Lipid droplets are indicated by black arrows. H, Gross morphological images of zebrafish at 50-hpf. The zebrafish pericardium (yellow zone) and heart (red zone) are indicated. I, Quantification of the pericardial area of embryos in H (n=10 embryos per group). *P<0.05; ***P<0.001; ****P<0.0001.
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