Transfer of a Mouse Artificial Chromosome into Spermatogonial Stem Cells Generates Transchromosomic Mice
The introduction of megabase-sized large DNA fragments into the germline has been a difficult task. Although microcell-mediated chromosome transfer into mouse embryonic stem cells (ESCs) allows the production of transchromosomic mice, ESCs have unstable karyotypes and germline transmission is unreli...
Main Authors: | , , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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Elsevier
2017-10-01
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Series: | Stem Cell Reports |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671117303697 |
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author | Takashi Shinohara Kanako Kazuki Narumi Ogonuki Hiroko Morimoto Shogo Matoba Kei Hiramatsu Kazuhisa Honma Teruhiko Suzuki Takahiko Hara Atsuo Ogura Mitsuo Oshimura Mito Kanatsu-Shinohara Yasuhiro Kazuki |
author_facet | Takashi Shinohara Kanako Kazuki Narumi Ogonuki Hiroko Morimoto Shogo Matoba Kei Hiramatsu Kazuhisa Honma Teruhiko Suzuki Takahiko Hara Atsuo Ogura Mitsuo Oshimura Mito Kanatsu-Shinohara Yasuhiro Kazuki |
author_sort | Takashi Shinohara |
collection | DOAJ |
description | The introduction of megabase-sized large DNA fragments into the germline has been a difficult task. Although microcell-mediated chromosome transfer into mouse embryonic stem cells (ESCs) allows the production of transchromosomic mice, ESCs have unstable karyotypes and germline transmission is unreliable by chimera formation. As spermatogonial stem cells (SSCs) are the only stem cells in the germline, they represent an attractive target for germline modification. Here, we report successful transfer of a mouse artificial chromosome (MAC) into mouse germline stem cells (GSCs), cultured spermatogonia enriched for SSCs. MAC-transferred GSCs maintained the host karyotype and MAC more stably than ESCs, which have significant variation in chromosome number. Moreover, MAC-transferred GSCs produced transchromosomic mice following microinjection into the seminiferous tubules of infertile recipients. Successful transfer of MACs to GSCs overcomes the problems associated with ESC-mediated germline transmission and provides new possibilities in germline modification. |
first_indexed | 2024-12-22T08:12:25Z |
format | Article |
id | doaj.art-30cd4abc82c14a58823f2614f56dbfef |
institution | Directory Open Access Journal |
issn | 2213-6711 |
language | English |
last_indexed | 2024-12-22T08:12:25Z |
publishDate | 2017-10-01 |
publisher | Elsevier |
record_format | Article |
series | Stem Cell Reports |
spelling | doaj.art-30cd4abc82c14a58823f2614f56dbfef2022-12-21T18:32:59ZengElsevierStem Cell Reports2213-67112017-10-01941180119110.1016/j.stemcr.2017.08.012Transfer of a Mouse Artificial Chromosome into Spermatogonial Stem Cells Generates Transchromosomic MiceTakashi Shinohara0Kanako Kazuki1Narumi Ogonuki2Hiroko Morimoto3Shogo Matoba4Kei Hiramatsu5Kazuhisa Honma6Teruhiko Suzuki7Takahiko Hara8Atsuo Ogura9Mitsuo Oshimura10Mito Kanatsu-Shinohara11Yasuhiro Kazuki12Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo-ku, Kyoto 606-8501, JapanChromosome Engineering Research Center (CERC), Tottori University, 86 Nishicho, Yonago 683-8503, JapanRIKEN BioResource Center, Tsukuba 305-0074, JapanDepartment of Molecular Genetics, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo-ku, Kyoto 606-8501, JapanRIKEN BioResource Center, Tsukuba 305-0074, JapanDepartment of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Yonago 683-8503, JapanDepartment of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Yonago 683-8503, JapanStem Cell Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, JapanStem Cell Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, JapanRIKEN BioResource Center, Tsukuba 305-0074, JapanChromosome Engineering Research Center (CERC), Tottori University, 86 Nishicho, Yonago 683-8503, JapanDepartment of Molecular Genetics, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo-ku, Kyoto 606-8501, JapanChromosome Engineering Research Center (CERC), Tottori University, 86 Nishicho, Yonago 683-8503, JapanThe introduction of megabase-sized large DNA fragments into the germline has been a difficult task. Although microcell-mediated chromosome transfer into mouse embryonic stem cells (ESCs) allows the production of transchromosomic mice, ESCs have unstable karyotypes and germline transmission is unreliable by chimera formation. As spermatogonial stem cells (SSCs) are the only stem cells in the germline, they represent an attractive target for germline modification. Here, we report successful transfer of a mouse artificial chromosome (MAC) into mouse germline stem cells (GSCs), cultured spermatogonia enriched for SSCs. MAC-transferred GSCs maintained the host karyotype and MAC more stably than ESCs, which have significant variation in chromosome number. Moreover, MAC-transferred GSCs produced transchromosomic mice following microinjection into the seminiferous tubules of infertile recipients. Successful transfer of MACs to GSCs overcomes the problems associated with ESC-mediated germline transmission and provides new possibilities in germline modification.http://www.sciencedirect.com/science/article/pii/S2213671117303697spermatogenesiskaryotypeartificial chromosomespermatogonia |
spellingShingle | Takashi Shinohara Kanako Kazuki Narumi Ogonuki Hiroko Morimoto Shogo Matoba Kei Hiramatsu Kazuhisa Honma Teruhiko Suzuki Takahiko Hara Atsuo Ogura Mitsuo Oshimura Mito Kanatsu-Shinohara Yasuhiro Kazuki Transfer of a Mouse Artificial Chromosome into Spermatogonial Stem Cells Generates Transchromosomic Mice Stem Cell Reports spermatogenesis karyotype artificial chromosome spermatogonia |
title | Transfer of a Mouse Artificial Chromosome into Spermatogonial Stem Cells Generates Transchromosomic Mice |
title_full | Transfer of a Mouse Artificial Chromosome into Spermatogonial Stem Cells Generates Transchromosomic Mice |
title_fullStr | Transfer of a Mouse Artificial Chromosome into Spermatogonial Stem Cells Generates Transchromosomic Mice |
title_full_unstemmed | Transfer of a Mouse Artificial Chromosome into Spermatogonial Stem Cells Generates Transchromosomic Mice |
title_short | Transfer of a Mouse Artificial Chromosome into Spermatogonial Stem Cells Generates Transchromosomic Mice |
title_sort | transfer of a mouse artificial chromosome into spermatogonial stem cells generates transchromosomic mice |
topic | spermatogenesis karyotype artificial chromosome spermatogonia |
url | http://www.sciencedirect.com/science/article/pii/S2213671117303697 |
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