Fig. 1

CRISPR Cas-9-mediated Kcnh2 mutation leads to altered Kcnh2 expression patterns. (A). Topology of K_v11.1 protein denoting the site of 7bp-deletion mutation in S5 of the pore domain. (B). RNA sequencing indicates altered total Kcnh2 expression in WT and Kcnh2^{(+/7bp−del)} rabbit heart and brain tissue. WT left ventricle N = 10 rabbits, WT brainstem N = 11 rabbits, Kcnh2^{(+/7bp−del)} left ventricle N = 10 rabbits, Kcnh2^{(+/7bp−del)} brainstem N = 13 rabbits. (C). Oxford Nanopore Technology (ONT) sequencing of WT and mutant Kcnh2 amplicons generated using RNA extracted from mutant rabbits (N = 3). (D). qPCR resuls for region-specific expression of (1) Total (WT + mutant), (2) WT, and (3) 7bp-del mutant Kcnh2 transcripts in WT (N = 7) vs. mutant (N = 7) rabbit tissue. All qPCR data is normalized to plate normalization factor (described in results). Statistical analyses: performed one-way ANOVA (B, C) and unpaired t-tests (D1, 2). *, p < 0.05; **, p < 0.01; ****, p < 0.0001. Actb: beta-actin