Construction of stable mouse artificial chromosome from native mouse chromosome 10 for generation of transchromosomic mice

Abstract Mammalian artificial chromosomes derived from native chromosomes have been applied to biomedical research and development by generating cell sources and transchromosomic (Tc) animals. Human artificial chromosome (HAC) is a precedent chromosomal vector which achieved generation of valuable h...

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Autores principales: Satoshi Abe, Kazuhisa Honma, Akane Okada, Kanako Kazuki, Hiroshi Tanaka, Takeshi Endo, Kayoko Morimoto, Takashi Moriwaki, Shusei Hamamichi, Yuji Nakayama, Teruhiko Suzuki, Shoko Takehara, Mitsuo Oshimura, Yasuhiro Kazuki
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/980a4802a45243dab043c205122e0872
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spelling oai:doaj.org-article:980a4802a45243dab043c205122e08722021-12-02T19:16:11ZConstruction of stable mouse artificial chromosome from native mouse chromosome 10 for generation of transchromosomic mice10.1038/s41598-021-99535-y2045-2322https://doaj.org/article/980a4802a45243dab043c205122e08722021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-99535-yhttps://doaj.org/toc/2045-2322Abstract Mammalian artificial chromosomes derived from native chromosomes have been applied to biomedical research and development by generating cell sources and transchromosomic (Tc) animals. Human artificial chromosome (HAC) is a precedent chromosomal vector which achieved generation of valuable humanized animal models for fully human antibody production and human pharmacokinetics. While humanized Tc animals created by HAC vector have attained significant contributions, there was a potential issue to be addressed regarding stability in mouse tissues, especially highly proliferating hematopoietic cells. Mouse artificial chromosome (MAC) vectors derived from native mouse chromosome 11 demonstrated improved stability, and they were utilized for humanized Tc mouse production as a standard vector. In mouse, however, stability of MAC vector derived from native mouse chromosome other than mouse chromosome 11 remains to be evaluated. To clarify the potential of mouse centromeres in the additional chromosomes, we constructed a new MAC vector from native mouse chromosome 10 to evaluate the stability in Tc mice. The new MAC vector was transmitted through germline and stably maintained in the mouse tissues without any apparent abnormalities. Through this study, the potential of additional mouse centromere was demonstrated for Tc mouse production, and new MAC is expected to be used for various applications.Satoshi AbeKazuhisa HonmaAkane OkadaKanako KazukiHiroshi TanakaTakeshi EndoKayoko MorimotoTakashi MoriwakiShusei HamamichiYuji NakayamaTeruhiko SuzukiShoko TakeharaMitsuo OshimuraYasuhiro KazukiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Satoshi Abe
Kazuhisa Honma
Akane Okada
Kanako Kazuki
Hiroshi Tanaka
Takeshi Endo
Kayoko Morimoto
Takashi Moriwaki
Shusei Hamamichi
Yuji Nakayama
Teruhiko Suzuki
Shoko Takehara
Mitsuo Oshimura
Yasuhiro Kazuki
Construction of stable mouse artificial chromosome from native mouse chromosome 10 for generation of transchromosomic mice
description Abstract Mammalian artificial chromosomes derived from native chromosomes have been applied to biomedical research and development by generating cell sources and transchromosomic (Tc) animals. Human artificial chromosome (HAC) is a precedent chromosomal vector which achieved generation of valuable humanized animal models for fully human antibody production and human pharmacokinetics. While humanized Tc animals created by HAC vector have attained significant contributions, there was a potential issue to be addressed regarding stability in mouse tissues, especially highly proliferating hematopoietic cells. Mouse artificial chromosome (MAC) vectors derived from native mouse chromosome 11 demonstrated improved stability, and they were utilized for humanized Tc mouse production as a standard vector. In mouse, however, stability of MAC vector derived from native mouse chromosome other than mouse chromosome 11 remains to be evaluated. To clarify the potential of mouse centromeres in the additional chromosomes, we constructed a new MAC vector from native mouse chromosome 10 to evaluate the stability in Tc mice. The new MAC vector was transmitted through germline and stably maintained in the mouse tissues without any apparent abnormalities. Through this study, the potential of additional mouse centromere was demonstrated for Tc mouse production, and new MAC is expected to be used for various applications.
format article
author Satoshi Abe
Kazuhisa Honma
Akane Okada
Kanako Kazuki
Hiroshi Tanaka
Takeshi Endo
Kayoko Morimoto
Takashi Moriwaki
Shusei Hamamichi
Yuji Nakayama
Teruhiko Suzuki
Shoko Takehara
Mitsuo Oshimura
Yasuhiro Kazuki
author_facet Satoshi Abe
Kazuhisa Honma
Akane Okada
Kanako Kazuki
Hiroshi Tanaka
Takeshi Endo
Kayoko Morimoto
Takashi Moriwaki
Shusei Hamamichi
Yuji Nakayama
Teruhiko Suzuki
Shoko Takehara
Mitsuo Oshimura
Yasuhiro Kazuki
author_sort Satoshi Abe
title Construction of stable mouse artificial chromosome from native mouse chromosome 10 for generation of transchromosomic mice
title_short Construction of stable mouse artificial chromosome from native mouse chromosome 10 for generation of transchromosomic mice
title_full Construction of stable mouse artificial chromosome from native mouse chromosome 10 for generation of transchromosomic mice
title_fullStr Construction of stable mouse artificial chromosome from native mouse chromosome 10 for generation of transchromosomic mice
title_full_unstemmed Construction of stable mouse artificial chromosome from native mouse chromosome 10 for generation of transchromosomic mice
title_sort construction of stable mouse artificial chromosome from native mouse chromosome 10 for generation of transchromosomic mice
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/980a4802a45243dab043c205122e0872
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