Extended Data Fig. 5: Sarcoplasmic misaccumulation of RBM20-R636S in inherited RBM20-DCM and splicing speckle amplification in ischemic DCM.
From: Dysregulated ribonucleoprotein granules promote cardiomyopathy in RBM20 gene-edited pigs
a, Expanded views of (Fig. 3a, third panel) demonstrating RBM20 IHC at increasing magnification power (10x, 20X and 40X) highlighting intense sarcoplasmic and nuclear expression in myocardium of DCM patient, an R636S mutant allele carrier, analogous to the HTZ gene-edited RBM20 pig (Fig. 1c, central panel). Automated IHC repeated three times in this patient’s myocardium yielded results. Scale bars, μm. b, Human end-stage ischemic cardiomyopathy myocardium stained by H&E histochemistry (left hand panel) comparing size of cardiomyocyte nuclei (white arrows) to non-cardiomyocytes (yellow arrow), FISH for human chromosomes 6 (green) and 8 (red) with DAPI highlighting advanced HF-associated polyploidy (central panel) and, correspondingly, amplification of transcriptionally-active RBM20 nuclear splicing speckles, each demonstrating a TTN gene locus on a human chromosome 2 by IF-IHC (right hand panel). Each result is representative of experiments repeated three times. Scale bars, μm.
