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© 2020, Kazuki et al. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

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.

Details

Title
A non-mosaic transchromosomic mouse model of Down syndrome carrying the long arm of human chromosome 21
Author
Yasuhiro, Kazuki; Gao, Feng J; Li, Yicong; Moyer, Anna J; Devenney, Benjamin; Hiramatsu Kei; Miyagawa-Tomita Sachiko; Abe, Satoshi; Kanako, Kazuki; Kajitani Naoyo; Uno Narumi; Takehara Shoko; Takiguchi Masato; Yamakawa Miho; Hasegawa Atsushi; Shimizu Ritsuko; Matsukura Satoko; Noda Naohiro; Narumi, Ogonuki; Inoue Kimiko; Matoba Shogo; Ogura Atsuo; Florea, Liliana D; Savonenko Alena; Xiao Meifang; Wu, Dan; Batista Denise AS; Yang, Junhua; Qiu Zhaozhu; Singh, Nandini; Richtsmeier, Joan T; Takeuchi, Takashi; Oshimura Mitsuo; Reeves, Roger H
University/institution
U.S. National Institutes of Health/National Library of Medicine
Publication year
2020
Publication date
2020
Publisher
eLife Sciences Publications Ltd.
e-ISSN
2050084X
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2429406772
Copyright
© 2020, Kazuki et al. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.