Establishment of mouse line showing inducible priapism‐like phenotypes

Autor: Daiki Hashimoto, Kota Fujimoto, Shin Morioka, Shinya Ayabe, Tomoya Kataoka, Ryutaro Fukumura, Yuko Ueda, Mizuki Kajimoto, Taiju Hyuga, Kentaro Suzuki, Isao Hara, Shinichi Asamura, Shigeharu Wakana, Atsushi Yoshiki, Yoichi Gondo, Masaru Tamura, Takehiko Sasaki, Gen Yamada
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Reproductive Medicine and Biology, Vol 21, Iss 1, Pp n/a-n/a (2022)
Druh dokumentu: article
ISSN: 1447-0578
1445-5781
DOI: 10.1002/rmb2.12472
Popis: Abstract 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 PITPα. Conclusions Our findings suggest that the current mutant is a mouse model for priapism and abnormalities in PI signaling pathways through PITPα may lead to priapism providing an attractive novel therapeutic target in its treatment.
Databáze: Directory of Open Access Journals
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