Pitx2 haploinsufficiency rescues Tbx5 haploinsufficiency in mice

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Fig. 4. Pitx2 haploinsufficiency rescues Tbx5 haploinsufficiency in mice. Pitx2 haploinsufficiency rescues Tbx5 haploinsufficiency in mice. (A) Relative transcript expression by qPCR in the left atria from Pitx2 and Tbx5 heterozygotes and Tbx5;Pitx2 compound heterozygotes. Data are means ± SEM normalized to R26CreERt2 mice (set as 1) (n = 11 R26CreERt2; n = 15 Tbx5fl/+;R26CreERt2; n = 4 Pitx2fl/+;R26CreERt2; n = 8 Tbx5fl/+;Pitx2fl/+;R26CreERt2). *P < 0.05, two-tailed t test. Experiments were performed in technical triplicate. (B) Representative Poincaré plot of RR interval versus the subsequent RR + 1 interval (n = 7 R26CreERt2, n = 6 Tbx5fl/+;R26CreERt2, n = 9 Pitx2fl/+;R26CreERt2, and n = 7 Tbx5fl/+;Pitx2fl/+;R26CreERt2). (C) P-wave duration and PR interval calculated from ambulatory telemetry ECG recordings from mice in (B). P values were determined by two-tailed t test. Data are means ± SEM. (D) Representative AP recordings from atrial myocytes isolated from R26CreERt2, Tbx5fl/+;R26CreERt2, Pitx2fl/+;R26CreERt2, and Tbx5fl/+;Pitx2fl/+;R26CreERt2 mice. RMP, APA, APD50, and APD90 repolarization were determined from n > 3 animals per group (n = 14 R26CreERt2 cells, n = 15 Tbx5fl/+;R26CreERt2, n = 14 Pitx2fl/+;R26CreERt2, and n = 13 Tbx5fl/+;Pitx2fl/+;R26CreERt2). P values were determined versus R26CreERT2 controls. Inappropriate depolarization P values were measured by two-tailed Fisher’s exact test; APD90 and APD50 were determined by two-tailed t test. (E) Pacing induction by intra-atrial pacing of R26CreERt2 (n = 10), Tbx5fl/+;R26CreERt2 (n = 7), Pitx2fl/+;R26CreERt2 (n = 5), and Tbx5fl/+;Pitx2fl/+;R26CreERt2 (n = 7) mice. P values were determined by two-tailed Fisher’s exact test. Rangarajan D. Nadadur et al., Sci Transl Med 2016;8:354ra115 Published by AAAS