Cre ert2

All animal studies and experimental procedures were performed according to the German animal care and ethics legislation and had been approved by the local government authority, the Committee on Research Animal Care, Regierungspräsidium Freiburg (G11/51 and X10/10H). The Mof^{fl/fl (ref.13 (link))} and Nphs2-Cre mice^{57 (link)} strains have been previously described. Gt(ROSA)26Sor^{tm4(ACTB-tdTomato,-EGFP)Luo/J} and Cre-ERT2 mice were sourced from the Jackson Laboratory (JAX, Bar Harbor, ME, USA). All mice were maintained on a C57BL/6 background, kept under a 12-h light and dark cycle, and water and standard chow were available ad libitum. Drosophila melanogaster stocks were maintained on standard cornmeal molasses agar food at 25 °C. Experiments were performed at 29 °C for maximal efficiency of the GAL4/UAS-System. Sns-GCN-GAL4 (gift from Susan Abmayr) was used for targeted expression of UAS-Mof-RNA interference (VDRC TiD 105370).

C57BL/6 J wild type mice (4–6months), SIRT1^flox/flox mice (stock number 008041), and CreER^T2 (stock number 005657) mice were from Jackson Laboratory. Cardiomyocyte specific deletion of the SIRT1 gene mouse was generated by breeding SIRT1^flox/flox mice with transgenic mice that carried an autosomally integrated Cre gene driven by the cardiac-specific alpha-myosin heavy chain promoter (αMHC) (CreER^T2). The inducible cardiac-specific SIRT1 knockout (icSIRT1 KO) mice were generated by Tamoxifen injection (0.04 mg/g, i.p. 5 days) of CreER^T2-SIRT1^flox/flox (12 weeks old) mice, and SIRT1^flox/flox mice (12 weeks old) with Tamoxifen injection were used for control groups. Cardiac-specific deletion of the PDHa1 gene was also generated by breeding PDH E1α^flox/flox mice [37 ] with transgenic mice that carried an autosomally integrated Cre gene driven by the cardiac-specific aMHC (CreER^T2). The inducible cardiac-specific PDH E1α knockout (icPDH E1α KO) mice were generated by Tamoxifen injection (0.04 mg/g, ip 5 days), and PDH E1α^flox/flox (12 weeks old) mice with Tamoxifen injection were used for control groups. The genotying details were described in the Supplementary material online. All animal experiments were performed in compliance with NIH guidelines. And All animal protocols in this study were approved by the University of South Florida Institutional Animal Care and Use Committee.