Figure 1 .

FXN-depleted hearts exhibit normal contractility but are smaller. (A) Experimental model. Mice harbored a whole body-wide Doxy-inducible shRNA construct targeting Fxn (TG mice). Doxy (200 p.p.m.) was delivered in the chow. Both TG and WT mice (WT littermates) received the Doxy-dosed diet. (B) Representative immunoblots of FXN and GRB2 (loading control) in heart lysates from WT and TG mice and quantification (n = 7/genotype). (C) Iron homeostasis in heart lysates, determined by immunoblot (left panels: TFR, FPN1, FTH, with GRB2 as loading control) and qPCR (Tfrc). Bar charts: mRNA levels of Tfrc, normalized to Actb (β-actin) and expressed relative to WT, value = 1 means no change, (n = 12 WT/10 TG) and protein levels of TFR, FPN1 and FTH (n = 4–7 WT/5 TG). (D) Upper: Sections from heart stained with PPB to reveal iron deposition. Lower: Quantification of number of iron deposits per area (353 μm × 264 μm), (n = 7 WT/4 TG). (E) Upper: Cross-sections from hearts stained with MT to detect collagen as a measure of fibrosis. Lower: Quantification of area of collagen (%) from heart cross-sections (n = 7 WT/4 TG). (F) BW, TL, HW, HW/TL (n = 7/genotype) and CSA of cardiomyocytes (n = 7 WT/4 TG). (G) Transcript levels [normalized to Actb (β-actin) and expressed relative to WT] of Myh6 (α-MHC) and Myh7 (β-MHC) (n = 11–12/genotype; points are values from each sample). (B–G): Values are mean ± standard error of mean (SEM). Statistical comparison was by unpaired t-test; ^*P < 0.05, ^**P < 0.01, ^***P < 0.001. N.S.: not significant.