The Mc4r gene is responsible for the development of experimentally induced testicular teratomas
Abstract Teratomas in mice, composed of different tissue types, are derived from primordial germ cells in the fetal gonads. Previously, we identified a locus responsible for experimental testicular teratoma (ETT) formation on chromosome 18, referred to as ett1. The strongest candidate sequence in th...
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| Format: | Article |
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Nature Portfolio
2023-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-32784-1 |
| _version_ | 1797832098440019968 |
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| author | Syunsuke Seki Kaoru Ohura Takehiro Miyazaki Abdullah An Naser Shuji Takabayashi Eisei Tsutsumi Toshinobu Tokumoto |
| author_facet | Syunsuke Seki Kaoru Ohura Takehiro Miyazaki Abdullah An Naser Shuji Takabayashi Eisei Tsutsumi Toshinobu Tokumoto |
| author_sort | Syunsuke Seki |
| collection | DOAJ |
| description | Abstract Teratomas in mice, composed of different tissue types, are derived from primordial germ cells in the fetal gonads. Previously, we identified a locus responsible for experimental testicular teratoma (ETT) formation on chromosome 18, referred to as ett1. The strongest candidate sequence in the ett1 locus was found to be a missense mutation in the melanocortin 4 receptor (Mc4r), Mc4r G25S . We established a strain with a point mutation in the Mc4r gene in the ETT-nonsusceptible LT strain, called LT- Mc4r G25S , by genome editing. Surprisingly, highly developed ovarian teratomas (OTs), rather than testicular teratomas, appeared in the LT-Mc4r G25S strain. The results demonstrated that Mc4r is also one of the genes responsible for OT formation and suggested that missense mutations in Mc4r promote teratoma formation in both sexes. In this study, we performed ETT experiments in different host–graft combinations of the LT-Mc4r G25S and LT strains. Furthermore, the expression of MC4R in germ cells in the testis was demonstrated. Expression of Mc4r in testis was also confirmed by RT-PCR. The results demonstrated that MC4R is expressed in germ cells in the testis and that a point mutation in the Mc4r gene is responsible for ETT formation. |
| first_indexed | 2024-04-09T14:02:20Z |
| format | Article |
| id | doaj.art-877885b9489645fb936c03c5ea67bfb7 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T14:02:20Z |
| publishDate | 2023-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-877885b9489645fb936c03c5ea67bfb72023-05-07T11:12:40ZengNature PortfolioScientific Reports2045-23222023-05-011311910.1038/s41598-023-32784-1The Mc4r gene is responsible for the development of experimentally induced testicular teratomasSyunsuke Seki0Kaoru Ohura1Takehiro Miyazaki2Abdullah An Naser3Shuji Takabayashi4Eisei Tsutsumi5Toshinobu Tokumoto6Department of Bioscience, Faculty of Science, Shizuoka UniversityDepartment of Bioscience, Faculty of Science, Shizuoka UniversityIntegrated Bioscience Section, Graduate School of Science and Technology, National University Corporation Shizuoka UniversityDepartment of Bioscience, Faculty of Science, Shizuoka UniversityLaboratory Animal Facilities & Services, Preeminent Medical Photonics Education & Research Center, Hamamatsu University School of MedicineBiological Science Course, Department of Science, Graduate School of Integrated Science and Technology, Shizuoka UniversityDepartment of Bioscience, Faculty of Science, Shizuoka UniversityAbstract Teratomas in mice, composed of different tissue types, are derived from primordial germ cells in the fetal gonads. Previously, we identified a locus responsible for experimental testicular teratoma (ETT) formation on chromosome 18, referred to as ett1. The strongest candidate sequence in the ett1 locus was found to be a missense mutation in the melanocortin 4 receptor (Mc4r), Mc4r G25S . We established a strain with a point mutation in the Mc4r gene in the ETT-nonsusceptible LT strain, called LT- Mc4r G25S , by genome editing. Surprisingly, highly developed ovarian teratomas (OTs), rather than testicular teratomas, appeared in the LT-Mc4r G25S strain. The results demonstrated that Mc4r is also one of the genes responsible for OT formation and suggested that missense mutations in Mc4r promote teratoma formation in both sexes. In this study, we performed ETT experiments in different host–graft combinations of the LT-Mc4r G25S and LT strains. Furthermore, the expression of MC4R in germ cells in the testis was demonstrated. Expression of Mc4r in testis was also confirmed by RT-PCR. The results demonstrated that MC4R is expressed in germ cells in the testis and that a point mutation in the Mc4r gene is responsible for ETT formation.https://doi.org/10.1038/s41598-023-32784-1 |
| spellingShingle | Syunsuke Seki Kaoru Ohura Takehiro Miyazaki Abdullah An Naser Shuji Takabayashi Eisei Tsutsumi Toshinobu Tokumoto The Mc4r gene is responsible for the development of experimentally induced testicular teratomas Scientific Reports |
| title | The Mc4r gene is responsible for the development of experimentally induced testicular teratomas |
| title_full | The Mc4r gene is responsible for the development of experimentally induced testicular teratomas |
| title_fullStr | The Mc4r gene is responsible for the development of experimentally induced testicular teratomas |
| title_full_unstemmed | The Mc4r gene is responsible for the development of experimentally induced testicular teratomas |
| title_short | The Mc4r gene is responsible for the development of experimentally induced testicular teratomas |
| title_sort | mc4r gene is responsible for the development of experimentally induced testicular teratomas |
| url | https://doi.org/10.1038/s41598-023-32784-1 |
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