New mouse models for the analysis of cGMP signalling

The second messenger cGMP mediates beneficial and detrimental effects of nitric oxide and natriuretic peptides. Studies with conventional knockout mice showed that the cGMP-dependent protein kinase type I (cGKI) transduces many acute effects of cGMP, such as smooth muscle relaxation and inhibition of platelet aggregation. However, the short life expectancy of cGKI null mice precludes the analysis of long-term processes in adult mice. Recently, we have generated conditional tissue-specific cGKI knockout and rescue mice that can be studied throughout adulthood. These mouse models have uncovered previously unknown functions of cGMP/cGKI signalling in complex behavioural processes, such as object recognition, social discrimination and the regulation of sleep-wake activity. Moreover, a novel role of cGKI in erythrocyte death will be discussed.