Fig 9.
Relationship between cardiomyopathy, gap junction remodeling, and arrhythmic susceptibility in the DKO mice. (A to D) Heart sections from PGflox/flox/β-cateninflox/flox; Cre− (WT) and PGflox/flox/β-cateninflox/flox; Cre+ (DKO) mice were stained with acid fuchsin orange G at 3 (3W) (B), 5 (5W) (C), and 8 (8W) (D) weeks after Tam administration. Note the fibrotic response as early as 3 weeks in DKO hearts (B) compared with WT hearts (A). (E to L) Heart sections were immunostained for N-cadherin (Ncad, red) and connexin43 (Cx43, green) at 3 (F, J), 5 (G and K), and 8 (H and L) weeks, respectively, after Tam administration. Note the decreased localization of both Ncad and Cx43 at the intercalated disc (ID) as early as 3 weeks after Tam administration. Arrowheads denote remaining N-cadherin/Cx43 colocalization at the ID. Ejection fraction (M) and fractional shortening (N) of DKO and WT hearts at 3, 5, 8, and 12 weeks after Tam administration as determined by echocardiography. The incidence of ventricular fibrillation in DKO hearts following burst pacing protocol was not significantly different at 3 (0/4) or 5 (1/5) weeks after Tam administration compared to that in the WT (0/10). However, the percentage of DKO hearts susceptible to induced arrhythmia at 8 (4/5) and 12 (8/11) weeks after Tam administration differed compared to the results for DKO mice at 3 weeks after Tam administration. *, P < 0.05; **, P < 0.01; ***, P < 0.001.