Fig. 8.

Biological network analysis of the SS down-regulated genes in the heart showed dramatic loss of expression of an extensive set of genes associated with maintenance of the electrophysiological and structural integrity of the heart. RNAseq showed that 31 ion channel genes and genes associated with electrophysiologic function were down-regulated in Berk-SS mouse myocardium compared with WT (n = 3 WT and 3 in Berk-SS). The seven key down-regulated genes (yellow: CPT1A, CPT2, SCN4B, AKAP9, SCN4A, KCNJ2, CACNA1S) are associated with arrhythmias and sudden cardiac death. The cardiac networks they affect and how they interact with the rest of the down-regulated genes associated with rhythm dysfunction, including prolonged QTc, are shown.