Germ cell depletion using HSV-TK in mouse testes
Abstract Germ cell transplantation is useful for the study of male germ cells and the generation of genetically modified animals. For transplantation, germ cell-free hosts generated using anticancer drug treatment, irradiation exposure, or genetic mutation are required. In this study, we aimed to de...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-03-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-93325-6 |
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| author | Constance Dollet Miyuki Shindo Shun Takahashi Kento Ito Tomoo Eto Toshiaki Watanabe |
| author_facet | Constance Dollet Miyuki Shindo Shun Takahashi Kento Ito Tomoo Eto Toshiaki Watanabe |
| author_sort | Constance Dollet |
| collection | DOAJ |
| description | Abstract Germ cell transplantation is useful for the study of male germ cells and the generation of genetically modified animals. For transplantation, germ cell-free hosts generated using anticancer drug treatment, irradiation exposure, or genetic mutation are required. In this study, we aimed to develop a new system for germ cell depletion, more in compliance with the “3R” principles. For this purpose, we generated knock-in mice expressing a subtype of the herpes simplex virus type 1 thymidine kinase (HSV-TK30), reported to not induce infertility, unlike the original HSV-TK gene. Ganciclovir injection resulted in nearly complete abrogation of spermatogenesis. Furthermore, transplanted spermatogonial stem cells were differentiated into sperm in the host testes, and they gave rise to offspring. Therefore, the mice developed in this study enable the efficient removal of germ cells for germ cell transplantation in a manner more compliant with the 3R principles. |
| format | Article |
| id | doaj-art-2b912a4fed364685ae9e3c8fddcd83ee |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-2b912a4fed364685ae9e3c8fddcd83ee2025-08-20T02:41:31ZengNature PortfolioScientific Reports2045-23222025-03-0115111110.1038/s41598-025-93325-6Germ cell depletion using HSV-TK in mouse testesConstance Dollet0Miyuki Shindo1Shun Takahashi2Kento Ito3Tomoo Eto4Toshiaki Watanabe5Center for Regenerative Medicine, National Center for Child Health and DevelopmentCenter for Regenerative Medicine, National Center for Child Health and DevelopmentCenter for Regenerative Medicine, National Center for Child Health and DevelopmentCenter for Regenerative Medicine, National Center for Child Health and DevelopmentCentral Institute for Experimental Medicine and Life ScienceCenter for Regenerative Medicine, National Center for Child Health and DevelopmentAbstract Germ cell transplantation is useful for the study of male germ cells and the generation of genetically modified animals. For transplantation, germ cell-free hosts generated using anticancer drug treatment, irradiation exposure, or genetic mutation are required. In this study, we aimed to develop a new system for germ cell depletion, more in compliance with the “3R” principles. For this purpose, we generated knock-in mice expressing a subtype of the herpes simplex virus type 1 thymidine kinase (HSV-TK30), reported to not induce infertility, unlike the original HSV-TK gene. Ganciclovir injection resulted in nearly complete abrogation of spermatogenesis. Furthermore, transplanted spermatogonial stem cells were differentiated into sperm in the host testes, and they gave rise to offspring. Therefore, the mice developed in this study enable the efficient removal of germ cells for germ cell transplantation in a manner more compliant with the 3R principles.https://doi.org/10.1038/s41598-025-93325-6Germ cell transplantationSpermatogonial stem cellsHost miceTestesHSV-TKDDX4 |
| spellingShingle | Constance Dollet Miyuki Shindo Shun Takahashi Kento Ito Tomoo Eto Toshiaki Watanabe Germ cell depletion using HSV-TK in mouse testes Scientific Reports Germ cell transplantation Spermatogonial stem cells Host mice Testes HSV-TK DDX4 |
| title | Germ cell depletion using HSV-TK in mouse testes |
| title_full | Germ cell depletion using HSV-TK in mouse testes |
| title_fullStr | Germ cell depletion using HSV-TK in mouse testes |
| title_full_unstemmed | Germ cell depletion using HSV-TK in mouse testes |
| title_short | Germ cell depletion using HSV-TK in mouse testes |
| title_sort | germ cell depletion using hsv tk in mouse testes |
| topic | Germ cell transplantation Spermatogonial stem cells Host mice Testes HSV-TK DDX4 |
| url | https://doi.org/10.1038/s41598-025-93325-6 |
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