Extended Data Fig. 4: Pathological hypertrophy, polyploidy and abnormal mitochondria in HMZ pig myocardium.
From: Dysregulated ribonucleoprotein granules promote cardiomyopathy in RBM20 gene-edited pigs
a, Graphical comparison of body weight, heart weight, heart weight/body weight ratio and LV free wall thickness (hypertrophy) in WT and HMZ pigs at 16 weeks of age reported as graphs showing median, Q1, Q3 and range. N=number of individual pigs studied and significance calculated by two-sided Student’s t-test. b, Fluorescence in situ hybridization (FISH) for pig X-chromosome in HMZ male (XY) pig myocardium. Yellow circles highlight X-chromosome signals in nuclei with greater than diploid (one dot) genomic DNA content. This result is representative of three repeat FISH studies. Scale bar, μm. c, Time course study of H&E stained HMZ pig LV-myocardium at day-1, day-7 and 16-weeks highlighting progression of pathological hypertrophy, nuclear abnormalities, cellular disarray and fibrosis. Scale bar, μm. d, Analogous to heat map data presented in Fig. 2g (see blue arrow), RNA-seq alternative splicing scatter plot analysis of IMMT (mitofilin) comparing WT (green), HTZ (black) and HMZ (red) pig myocardium at 16 weeks, clustered dots (circled) highlight genotype-specific alternative splicing of IMMT pre-mRNA, n=number of individual pigs. Right hand panel, correlating with IMMT missplicing, TEM comparing mitochondrial ultrastructure highlighting abnormally shaped cristae (arrows) in HMZ versus WT myocardium at day-7 by TEM, with similar myocardial mitochondrial morphological abnormalities observed in three different HMZ piglets. Scale bar, μm.
