Erectile dysfunction in cyclic CMP-dependent kinase I-deficient mice

The generation of nitric oxide (NO) in penile erectile tissue and the subse quent elevation of cyclic GMP (cGMP) levels are important for normal penile erection. Current treatments of erectile dysfunction elevate either cGMP l evels by blocking cGMP degrading phosphodiesterase 5 or cyclic AMP (cAMP) l evels by intrapenile injection of prostaglandin E1. The molecular target or targets of cGMP in erectile tissue and the role of cAMP for normal penile erection are not known. Herein, we report that mice lacking cGMP-dependent kinase I (cGKI) have a very low ability to reproduce and that their corpora cavernosa fail to relax on activation of the NO/cCMP signaling cascade. El evation of cAMP by forskolin, however, induces similar relaxation in normal and cGKI-null corpus cavernosum. In addition, sperm derived from cGKI-null mice is normal, can undergo acrosomal reactions, and can efficiently ferti lize eggs. Altogether, these data identify cGKI as the downstream target of cGMP in erectile tissue and provide evidence that cAMP signaling cannot co mpensate for the absence of the cGMP/cGKI signaling cascade in vivo.