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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 medic...

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Autores principales: Hashimoto, Daiki, Fujimoto, Kota, Morioka, Shin, Ayabe, Shinya, Kataoka, Tomoya, Fukumura, Ryutaro, Ueda, Yuko, Kajimoto, Mizuki, Hyuga, Taiju, Suzuki, Kentaro, Hara, Isao, Asamura, Shinichi, Wakana, Shigeharu, Yoshiki, Atsushi, Gondo, Yoichi, Tamura, Masaru, Sasaki, Takehiko, Yamada, Gen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207557/
https://www.ncbi.nlm.nih.gov/pubmed/35765371
http://dx.doi.org/10.1002/rmb2.12472
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author Hashimoto, Daiki
Fujimoto, Kota
Morioka, Shin
Ayabe, Shinya
Kataoka, Tomoya
Fukumura, Ryutaro
Ueda, Yuko
Kajimoto, Mizuki
Hyuga, Taiju
Suzuki, Kentaro
Hara, Isao
Asamura, Shinichi
Wakana, Shigeharu
Yoshiki, Atsushi
Gondo, Yoichi
Tamura, Masaru
Sasaki, Takehiko
Yamada, Gen
author_facet Hashimoto, Daiki
Fujimoto, Kota
Morioka, Shin
Ayabe, Shinya
Kataoka, Tomoya
Fukumura, Ryutaro
Ueda, Yuko
Kajimoto, Mizuki
Hyuga, Taiju
Suzuki, Kentaro
Hara, Isao
Asamura, Shinichi
Wakana, Shigeharu
Yoshiki, Atsushi
Gondo, Yoichi
Tamura, Masaru
Sasaki, Takehiko
Yamada, Gen
author_sort Hashimoto, Daiki
collection PubMed
description 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.
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spelling pubmed-92075572022-06-27 Establishment of mouse line showing inducible priapism‐like phenotypes Hashimoto, Daiki Fujimoto, Kota Morioka, Shin Ayabe, Shinya Kataoka, Tomoya Fukumura, Ryutaro Ueda, Yuko Kajimoto, Mizuki Hyuga, Taiju Suzuki, Kentaro Hara, Isao Asamura, Shinichi Wakana, Shigeharu Yoshiki, Atsushi Gondo, Yoichi Tamura, Masaru Sasaki, Takehiko Yamada, Gen Reprod Med Biol Original Articles 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. John Wiley and Sons Inc. 2022-06-20 /pmc/articles/PMC9207557/ /pubmed/35765371 http://dx.doi.org/10.1002/rmb2.12472 Text en © 2022 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Hashimoto, Daiki
Fujimoto, Kota
Morioka, Shin
Ayabe, Shinya
Kataoka, Tomoya
Fukumura, Ryutaro
Ueda, Yuko
Kajimoto, Mizuki
Hyuga, Taiju
Suzuki, Kentaro
Hara, Isao
Asamura, Shinichi
Wakana, Shigeharu
Yoshiki, Atsushi
Gondo, Yoichi
Tamura, Masaru
Sasaki, Takehiko
Yamada, Gen
Establishment of mouse line showing inducible priapism‐like phenotypes
title Establishment of mouse line showing inducible priapism‐like phenotypes
title_full Establishment of mouse line showing inducible priapism‐like phenotypes
title_fullStr Establishment of mouse line showing inducible priapism‐like phenotypes
title_full_unstemmed Establishment of mouse line showing inducible priapism‐like phenotypes
title_short Establishment of mouse line showing inducible priapism‐like phenotypes
title_sort establishment of mouse line showing inducible priapism‐like phenotypes
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207557/
https://www.ncbi.nlm.nih.gov/pubmed/35765371
http://dx.doi.org/10.1002/rmb2.12472
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