Fig. 1. Cardiac specific gene deletion of RARα induces diastolic dysfunction.
(A) α-MHC-Cre-RARαfl/fl mice were treated with tamoxifen (0.5 mg/day) or vehicle for 4 days, at 6 wks of age, tissues were collected after 2 wks and PCR analysis of genomic DNA performed. Arrow indicates floxed and floxed out band. (B) Protein expression of RARα in hearts of WT and RARαKO mice, after 20 wks of gene deletion, was determined by Western blot and quantified by densitometry. *p<0.05 vs WT. Equal loading was verified by α-tubulin expression. (C) Adult cardiomyocytes were isolated from WT and RARαKO mice after 20 wks, protein expression of RARα determined. (D–F) Echocardiography was performed at the times indicated, before (0) and after gene deletion. (D) LVEF%; (E) E/A ratio and (F) cardiac output (CO). *p<0.05 vs age matched WT. (G–J) Cardiac catheterization was performed, dP/dtmax (G), dP/dtmin (H), LVEDP (I) and Tau (J) analyzed, in WT (n=10) and RARαKO mice (n=9) at 20 wks. *p<0.05 vs WT.