Effect of cardiomyocyte specific KO of AKT1 + AKT2 on gene expression profile of the heart. Mus musculus

In the mammalian heart AKT1 and AKT2 are the isoforms of the protein kinase AKT (protein kinase B) which are predominantly expressed. AKT isoforms exert common and specific functions in the field of metabolism, cellular growth, apoptosis and cell migration. To identify specific and common functions of AKT1 and AKT2 isoforms, we generated tamoxifen-inducible, cardiomyocyte-specific AKT1+AKT2 double knockout mice (iCMAKT – KO mice). Inactivation of AKT isoforms was achieved by application of 4-OH-tamoxifen, which activates an OH-Tx inducible cre-recombinase expressed under the control of the αMHC-promoter (αMHC-mercremer). Transgenic mice expressing only the αMHCmercremer construct were also treated with OH-Tx and served as controls. To identify alterations in cardiac gene expression due to AKT deletion we analyzed gene expression profiles of control hearts and iCMAKT1+2 hearts. Overall design: Gene expression of mouse hearts of inducible, cardiomyocyte-specific AKT1+AKT2 KO mice. Mice express a mercremer recombinase under control of the αMHC promotor. AKT1 and AKT2 genes have loxP-flanked exons6 and7 and exon 5 exon 6 , respectively. Control mice only express the MHCmercremer gene. For RNA isolation four hearts of control control mice and three double KO were used. At age of 3 month mice were treated with 500µg hydroxytamoxifen (OH-Tx) per day for 5 days to induce the specific KO of AKT alleles in cardiomyocytes. Control mice express the MHCmercremer construct and were treated with OH-Tx equally. For RNA isolation four hearts of control and KO mice were harvested from 3 month old male mice 10 days after induction with OH-Tx. RNA was isolated from heart apex. 3 month old male mice after 5 injections of 4OH-tamoxifen served as controls.