Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1784729558929375232 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9207557 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT hashimotodaiki establishmentofmouselineshowinginduciblepriapismlikephenotypes AT fujimotokota establishmentofmouselineshowinginduciblepriapismlikephenotypes AT moriokashin establishmentofmouselineshowinginduciblepriapismlikephenotypes AT ayabeshinya establishmentofmouselineshowinginduciblepriapismlikephenotypes AT kataokatomoya establishmentofmouselineshowinginduciblepriapismlikephenotypes AT fukumuraryutaro establishmentofmouselineshowinginduciblepriapismlikephenotypes AT uedayuko establishmentofmouselineshowinginduciblepriapismlikephenotypes AT kajimotomizuki establishmentofmouselineshowinginduciblepriapismlikephenotypes AT hyugataiju establishmentofmouselineshowinginduciblepriapismlikephenotypes AT suzukikentaro establishmentofmouselineshowinginduciblepriapismlikephenotypes AT haraisao establishmentofmouselineshowinginduciblepriapismlikephenotypes AT asamurashinichi establishmentofmouselineshowinginduciblepriapismlikephenotypes AT wakanashigeharu establishmentofmouselineshowinginduciblepriapismlikephenotypes AT yoshikiatsushi establishmentofmouselineshowinginduciblepriapismlikephenotypes AT gondoyoichi establishmentofmouselineshowinginduciblepriapismlikephenotypes AT tamuramasaru establishmentofmouselineshowinginduciblepriapismlikephenotypes AT sasakitakehiko establishmentofmouselineshowinginduciblepriapismlikephenotypes AT yamadagen establishmentofmouselineshowinginduciblepriapismlikephenotypes |