Establishment of mouse line showing inducible priapism-like phenotypes

Purpose Penile research is expected to reveal new targets for treatment and prevention of the complex mechanisms of its disorder including erectile dysfunction (ED). Thus, analyses of the molecular processes of penile ED and continuous erection as priapism are essential issues of reproductive medicine. Methods By performing mouse N-ethyl-N-nitrosourea mutagenesis and exome sequencing, we established a novel mouse line displaying protruded genitalia phenotype (PGP; priapism-like phenotype) and identified a novel Pitpna gene mutation for PGP. Extensive histological analyses on the Pitpna mutant and intracavernous pressure measurement (ICP) and liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI/MS)/MS analyses were performed. Results We evaluated the role of phospholipids during erection for the first time and showed the mutants of inducible phenotypes of priapism. Moreover, quantitative analysis using LC-ESI/MS/MS revealed that the level of phosphatidylinositol (PI) was significantly lower in the mutant penile samples. These results imply that PI may contribute to penile erection by PITP alpha. Conclusions Our findings suggest that the current mutant is a mouse model for priapism and abnormalities in PI signaling pathways through PITP alpha may lead to priapism providing an attractive novel therapeutic target in its treatment.

Automated summary

This study established a mouse model with protruded genitalia phenotype (PGP), similar to priapism, and identified a novel gene mutation for PGP. The researchers evaluated the role of phospholipids, specifically phosphatidylinositol (PI), during penile erection and found that abnormalities in the PI signaling pathway may contribute to priapism. These findings provide a potential novel therapeutic target for the treatment of priapism.