Question: 

For normal penile erection the NO/cGMP cascade is thought to be essential. There is an assumption that lack of NO/cGMP mediated effects leads to erectile dysfunction. This causes reduced fertility in male mice lacking key enzymes of the cascade. The disadvantage of several studies was the use of conventional knockouts resulting in complete loss of the enzyme and leading to reduced fitness of the animals.

Methods: 

We have generated mice lacking NO-GC (GCKO), a bottleneck enzyme of the cascade. We showed that lack of NO-GC resulted in arterial hypertension concomitant with a totally abolished NO responsiveness of vascular and gastrointestinal smooth muscle. Global deletion of a protein in mice does not allow identification of the cell/tissue type responsible for a certain phenotype. We therefore generated a mouse line in which NO-GC was specifically deleted in smooth muscle cells (SM-GCKO). These mice should provide more detailed information on the role of NO and cGMP with regards to smooth muscle relaxation.

Results: 

Here we examined the role of NO/cGMP signaling with regards to the smooth muscle relaxation of corpus cavernosum. NO failed to relax corpus cavernosum from GCKO in organ bath experiments. Similar results were observed in the corpus cavernosum of SM-GCKO mice. To our surprise the GCKO model were fertility and produce offspring by increasing the fitness of the animals with feeding of a fiber-free diet.

Conclusions: 

Our data show that deletion of NO-GC globally or exclusively in smooth muscle abolishes corpus cavernosum relaxation, but nevertheless, does not impair fertility in full GCKO animals.