TY - JOUR
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.
N1 - Funding Information:
We thank Toko Kurosaki, Yukako Sumida, Hiromichi Kohno, Masami Morimura, Kei Yoshida, Eri Kaneda, Akiko Ashiba, Dr. Kazuomi Nakamura, Rina Ohnishi, Yuwna Yakura, Etsuya Ueno, Dr. Yuichi Iida, Dr. Yoshiteru Kai, Motoshi Kimura, Chie Ishihara, Kiyoko Kawakami, and Chiga Igawa at Tottori University for their technical assistance; as well as Dr. Hiroyuki Kugoh, Dr. Masaharu Hiratsuka, Dr. Tetsuya Ohbayashi, Dr. Hiroyuki Satofuka, and Dr. Takahito Ohira at Tottori University, Dr. Ohmiya Yoshihiro at Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), and Dr. Shigeharu Wakana, Dr. Tamio Furuse, Dr. Ikuko Yamada at Technology and Development Team for Mouse Phenotype Analysis Japan Mouse Clinic, RIKEN BioResource Center (BRC) for critical discussions. This research was partly performed at the Tottori Bio Frontier managed by Tottori prefecture. The work was supported in part by JST CREST Grant Number JPMJCR18S4, Japan (YK), JSPS KAKENHI Grant Number 25221308 (MO), Public Health Grants R01HD038384 and R21HD098540 (RHR). Opinions expressed in this article are the authors’ own and do not necessarily reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government.
Funding Information:
We thank Toko Kurosaki, Yukako Sumida, Hiromichi Kohno, Masami Morimura, Kei Yoshida, Eri Kaneda, Akiko Ashiba, Dr. Kazuomi Nakamura, Rina Ohnishi, Yuwna Yakura, Etsuya Ueno, Dr. Yuichi Iida, Dr. Yoshiteru Kai, Motoshi Kimura, Chie Ishihara, Kiyoko Kawakami, and Chiga Igawa at Tottori University for their technical assistance; as well as Dr. Hiroyuki Kugoh, Dr. Masaharu Hiratsuka, Dr. Tetsuya Ohbayashi, Dr. Hiroyuki Satofuka, and Dr. Takahito Ohira at Tottori University, Dr. Ohmiya Yoshihiro at Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), and Dr. Shigeharu Wakana, Dr. Tamio Furuse, Dr. Ikuko Yamada at Technology and Development Team for Mouse Phenotype Analysis Japan Mouse Clinic, RIKEN BioResource Center (BRC) for critical discussions. This research was partly performed at the Tottori Bio Frontier managed by Tottori prefecture. The work was supported in part by JST CREST Grant Number JPMJCR18S4, Japan (YK), JSPS KAKENHI Grant Number 25221308 (MO), Public Health Grants R01HD038384 and R21HD098540 (RHR). Opinions expressed in this article are the authors? own and do not necessarily reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government.
Publisher Copyright:
© Kazuki et al.
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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U2 - 10.7554/eLife.56223
DO - 10.7554/eLife.56223
M3 - Article
C2 - 32597754
AN - SCOPUS:85087950054
SN - 2050-084X
VL - 9
SP - 1
EP - 29
JO - eLife
JF - eLife
M1 - e56223
ER -