A non-mosaic transchromosomic mouse model of down syndrome carrying the long arm of human chromosome 21

Yasuhiro Kazuki; Feng J. Gao; Yicong Li; Anna J. Moyer; Benjamin Devenney; Kei Hiramatsu; Sachiko Miyagawa-Tomita; Satoshi Abe; Kanako Kazuki; Naoyo Kajitani; Narumi Uno; Shoko Takehara; Masato Takiguchi; Miho Yamakawa; Atsushi Hasegawa; Ritsuko Shimizu; Satoko Matsukura; Naohiro Noda; Narumi Ogonuki; Kimiko Inoue; Shogo Matoba; Atsuo Ogura; Liliana D. Florea; Alena Savonenko; Meifang Xiao; Dan Wu; Denise A.S. Batista; Junhua Yang; Zhaozhu Qiu; Nandini Singh; Joan T. Richtsmeier; Takashi Takeuchi; Mitsuo Oshimura; Roger H. Reeves

doi:10.7554/eLife.56223

A non-mosaic transchromosomic mouse model of down syndrome carrying the long arm of human chromosome 21

Yasuhiro Kazuki, Feng J. Gao, Yicong Li, Anna J. Moyer, Benjamin Devenney, Kei Hiramatsu, Sachiko Miyagawa-Tomita, Satoshi Abe, Kanako Kazuki, Naoyo Kajitani, Narumi Uno, Shoko Takehara, Masato Takiguchi, Miho Yamakawa, Atsushi Hasegawa, Ritsuko Shimizu, Satoko Matsukura, Naohiro Noda, Narumi Ogonuki, Kimiko InoueShogo Matoba, Atsuo Ogura, Liliana D. Florea, Alena Savonenko, Meifang Xiao, Dan Wu, Denise A.S. Batista, Junhua Yang, Zhaozhu Qiu, Nandini Singh, Joan T. Richtsmeier, Takashi Takeuchi, Mitsuo Oshimura, Roger H. Reeves

School of Medicine

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Animal models of Down syndrome (DS), trisomic for human chromosome 21 (HSA21) genes or orthologs, provide insights into better understanding and treatment options. The only existing transchromosomic (Tc) mouse DS model, Tc1, carries a HSA21 with over 50 protein coding genes (PCGs) disrupted. Tc1 is mosaic, compromising interpretation of results. Here, we “clone” the 34 MB long arm of HSA21 (HSA21q) as a mouse artificial chromosome (MAC). Through multiple steps of microcell-mediated chromosome transfer, we created a new Tc DS mouse model, Tc (HSA21q;MAC)1Yakaz (“TcMAC21”). TcMAC21 is not mosaic and contains 93% of HSA21q PCGs that are expressed and regulatable. TcMAC21 recapitulates many DS phenotypes including anomalies in heart, craniofacial skeleton and brain, molecular/cellular pathologies, and impairments in learning, memory and synaptic plasticity. TcMAC21 is the most complete genetic mouse model of DS extant and has potential for supporting a wide range of basic and preclinical research.

Original language	English (US)
Article number	e56223
Pages (from-to)	1-29
Number of pages	29
Journal	eLife
Volume	9
DOIs	https://doi.org/10.7554/eLife.56223
State	Published - Jun 2020

ASJC Scopus subject areas

General Neuroscience
General Biochemistry, Genetics and Molecular Biology
General Immunology and Microbiology

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Kazuki, Y., Gao, F. J., Li, Y., Moyer, A. J., Devenney, B., Hiramatsu, K., Miyagawa-Tomita, S., Abe, S., Kazuki, K., Kajitani, N., Uno, N., Takehara, S., Takiguchi, M., Yamakawa, M., Hasegawa, A., Shimizu, R., Matsukura, S., Noda, N., Ogonuki, N., ... Reeves, R. H. (2020). A non-mosaic transchromosomic mouse model of down syndrome carrying the long arm of human chromosome 21. eLife, 9, 1-29. Article e56223. https://doi.org/10.7554/eLife.56223

Kazuki, Y, Gao, FJ, Li, Y, Moyer, AJ, Devenney, B, Hiramatsu, K, Miyagawa-Tomita, S, Abe, S, Kazuki, K, Kajitani, N, Uno, N, Takehara, S, Takiguchi, M, Yamakawa, M, Hasegawa, A, Shimizu, R, Matsukura, S, Noda, N, Ogonuki, N, Inoue, K, Matoba, S, Ogura, A, Florea, LD, Savonenko, A, Xiao, M, Wu, D, Batista, DAS, Yang, J , Qiu, Z, Singh, N, Richtsmeier, JT, Takeuchi, T, Oshimura, M & Reeves, RH 2020, 'A non-mosaic transchromosomic mouse model of down syndrome carrying the long arm of human chromosome 21', eLife, vol. 9, e56223, pp. 1-29. https://doi.org/10.7554/eLife.56223

@article{6c80f911b014403389259b559541b2c3,

title = "A non-mosaic transchromosomic mouse model of down syndrome carrying the long arm of human chromosome 21",

abstract = "Animal models of Down syndrome (DS), trisomic for human chromosome 21 (HSA21) genes or orthologs, provide insights into better understanding and treatment options. The only existing transchromosomic (Tc) mouse DS model, Tc1, carries a HSA21 with over 50 protein coding genes (PCGs) disrupted. Tc1 is mosaic, compromising interpretation of results. Here, we “clone” the 34 MB long arm of HSA21 (HSA21q) as a mouse artificial chromosome (MAC). Through multiple steps of microcell-mediated chromosome transfer, we created a new Tc DS mouse model, Tc (HSA21q;MAC)1Yakaz (“TcMAC21”). TcMAC21 is not mosaic and contains 93% of HSA21q PCGs that are expressed and regulatable. TcMAC21 recapitulates many DS phenotypes including anomalies in heart, craniofacial skeleton and brain, molecular/cellular pathologies, and impairments in learning, memory and synaptic plasticity. TcMAC21 is the most complete genetic mouse model of DS extant and has potential for supporting a wide range of basic and preclinical research.",

author = "Yasuhiro Kazuki and Gao, {Feng J.} and Yicong Li and Moyer, {Anna J.} and Benjamin Devenney and Kei Hiramatsu and Sachiko Miyagawa-Tomita and Satoshi Abe and Kanako Kazuki and Naoyo Kajitani and Narumi Uno and Shoko Takehara and Masato Takiguchi and Miho Yamakawa and Atsushi Hasegawa and Ritsuko Shimizu and Satoko Matsukura and Naohiro Noda and Narumi Ogonuki and Kimiko Inoue and Shogo Matoba and Atsuo Ogura and Florea, {Liliana D.} and Alena Savonenko and Meifang Xiao and Dan Wu and Batista, {Denise A.S.} and Junhua Yang and Zhaozhu Qiu and Nandini Singh and Richtsmeier, {Joan T.} and Takashi Takeuchi and Mitsuo Oshimura and Reeves, {Roger H.}",

note = "Publisher Copyright: {\textcopyright} Kazuki et al.",

year = "2020",

month = jun,

doi = "10.7554/eLife.56223",

language = "English (US)",

volume = "9",

pages = "1--29",

journal = "eLife",

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T1 - A non-mosaic transchromosomic mouse model of down syndrome carrying the long arm of human chromosome 21

AU - Kazuki, Yasuhiro

AU - Gao, Feng J.

AU - Li, Yicong

AU - Moyer, Anna J.

AU - Devenney, Benjamin

AU - Hiramatsu, Kei

AU - Miyagawa-Tomita, Sachiko

AU - Abe, Satoshi

AU - Kazuki, Kanako

AU - Kajitani, Naoyo

AU - Uno, Narumi

AU - Takehara, Shoko

AU - Takiguchi, Masato

AU - Yamakawa, Miho

AU - Hasegawa, Atsushi

AU - Shimizu, Ritsuko

AU - Matsukura, Satoko

AU - Noda, Naohiro

AU - Ogonuki, Narumi

AU - Inoue, Kimiko

AU - Matoba, Shogo

AU - Ogura, Atsuo

AU - Florea, Liliana D.

AU - Savonenko, Alena

AU - Xiao, Meifang

AU - Wu, Dan

AU - Batista, Denise A.S.

AU - Yang, Junhua

AU - Qiu, Zhaozhu

AU - Singh, Nandini

AU - Richtsmeier, Joan T.

AU - Takeuchi, Takashi

AU - Oshimura, Mitsuo

AU - Reeves, Roger H.

PY - 2020/6

Y1 - 2020/6

N2 - Animal models of Down syndrome (DS), trisomic for human chromosome 21 (HSA21) genes or orthologs, provide insights into better understanding and treatment options. The only existing transchromosomic (Tc) mouse DS model, Tc1, carries a HSA21 with over 50 protein coding genes (PCGs) disrupted. Tc1 is mosaic, compromising interpretation of results. Here, we “clone” the 34 MB long arm of HSA21 (HSA21q) as a mouse artificial chromosome (MAC). Through multiple steps of microcell-mediated chromosome transfer, we created a new Tc DS mouse model, Tc (HSA21q;MAC)1Yakaz (“TcMAC21”). TcMAC21 is not mosaic and contains 93% of HSA21q PCGs that are expressed and regulatable. TcMAC21 recapitulates many DS phenotypes including anomalies in heart, craniofacial skeleton and brain, molecular/cellular pathologies, and impairments in learning, memory and synaptic plasticity. TcMAC21 is the most complete genetic mouse model of DS extant and has potential for supporting a wide range of basic and preclinical research.

AB - Animal models of Down syndrome (DS), trisomic for human chromosome 21 (HSA21) genes or orthologs, provide insights into better understanding and treatment options. The only existing transchromosomic (Tc) mouse DS model, Tc1, carries a HSA21 with over 50 protein coding genes (PCGs) disrupted. Tc1 is mosaic, compromising interpretation of results. Here, we “clone” the 34 MB long arm of HSA21 (HSA21q) as a mouse artificial chromosome (MAC). Through multiple steps of microcell-mediated chromosome transfer, we created a new Tc DS mouse model, Tc (HSA21q;MAC)1Yakaz (“TcMAC21”). TcMAC21 is not mosaic and contains 93% of HSA21q PCGs that are expressed and regulatable. TcMAC21 recapitulates many DS phenotypes including anomalies in heart, craniofacial skeleton and brain, molecular/cellular pathologies, and impairments in learning, memory and synaptic plasticity. TcMAC21 is the most complete genetic mouse model of DS extant and has potential for supporting a wide range of basic and preclinical research.

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JO - eLife

JF - eLife

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ER -

A non-mosaic transchromosomic mouse model of down syndrome carrying the long arm of human chromosome 21

Abstract

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