Breeding of AC knockout mice with transgenic mice expressing a cAMP sensor called pmEpac

The purpose is to cross breed our adenylyl cyclase (AC) type 5 and type 6 selective knockout mice with transgenic mice expressing a cAMP sensor at the cardiomyocyte membrane called pmEpac. Cross breeding these mice will not have any detrimental effects upon the offspring as both phenotypes are viable (normal). The generation of these mice will allow us to investigate receptor systems activating the cAMP signalling pathway without the need to virally transfect cAMP sensors into cardiomyocytes. These mice also offer the advantage of localizing the sensor to the plasma membrane where AC is located increasing sensitivity of the signal. Utilizing these mice we will be able to measure in real time beta-adrenergic receptor signaling and its regulation by inhibitory G protein and phosphodiesterases. These studies will contribute to our understanding how beta-adrenergic receptor signaling is regulated by inhibitory G protein which has a beneficial role in heart failure, thus results of these studies may lead to new treatment for heart failure.