Transfer of a Mouse Artificial Chromosome into Spermatogonial Stem Cells Generates Transchromosomic Mice
Author(s) -
Takashi Shinohara,
Kanako Kazuki,
Narumi Ogonuki,
Hiroko Morimoto,
Shogo Matoba,
Kei Hiramatsu,
Kazuhisa Honma,
Teruhiko Suzuki,
Takahiko Hara,
Atsuo Ogura,
Mitsuo Oshimura,
Mito KanatsuShinohara,
Yasuhiro Kazuki
Publication year - 2017
Publication title -
stem cell reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.207
H-Index - 76
ISSN - 2213-6711
DOI - 10.1016/j.stemcr.2017.08.012
Subject(s) - germline , biology , embryonic stem cell , stem cell , chimera (genetics) , reprogramming , genetics , microbiology and biotechnology , gene
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
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