Extended Data Fig. 1: Human RBM20-R636S germline genome editing strategy validated by cardiac MRI.

a, Cartoon depicting campaign to produce humanized R636S HTZ pigs by TALENs/HDR genome editing in WT pig fibroblasts followed by SCNT of gene-edited fibroblast nuclei into oocytes, implanted into surrogate sows. Crossbreeding of HTZ R636S germline gene-edited pigs produced HMZ F1 progeny with severe DCM/HF, the focus of this study. WT and R636S alleles signified by green and red color, respectively. A presentative piglet litter from this study is shown. b, Representative cardiac MRI images of 8 week-old HMZ pig showing end-diastolic and end-systolic frames in long and short axis with volumetrically calculated EF from ESV 60 ml and EDV 80 ml of 25% in this example. Yellow arrowhead, small pericardial effusion. c, Graph series comparing average heart rate (HR), calculated LVEF and corresponding LVEDV and LVESV (normalized to body surface area) by cardiac MRI at 8, 12 and 16 weeks of age in WT and HMZ pigs reported as median, Q1, Q3 and range with outliers as dots and n=number of individual pigs. Note that robust difference between WT and HMZ pigs at 8 weeks did not achieve statistical significance because of WT n=2 while later time points showed no statistical difference between WT and HMZ pigs. HMZ LVEDV increases with age but LVESV decreases even more explaining the normalization of LVEF, despite ventricular enlargement, in HMZ from 8 to 16 weeks.