A non-mosaic transchromosomic mouse model of Down syndrome carrying the long arm of human chromosome 21-Reference-Cited by-同舟云学术

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

Published:2020-06-29 Issue: Volume:9 Page:
ISSN:2050-084X
Container-title:eLife
language:en
Short-container-title:

Author:

Kazuki Yasuhiro¹²^ORCID,Gao Feng J³^ORCID,Li Yicong³,Moyer Anna J³⁴,Devenney Benjamin³,Hiramatsu Kei¹,Miyagawa-Tomita Sachiko⁵⁶,Abe Satoshi²,Kazuki Kanako²,Kajitani Naoyo²,Uno Narumi¹,Takehara Shoko²,Takiguchi Masato¹,Yamakawa Miho²,Hasegawa Atsushi⁷,Shimizu Ritsuko⁷,Matsukura Satoko⁸,Noda Naohiro⁸,Ogonuki Narumi⁹,Inoue Kimiko⁹,Matoba Shogo⁹,Ogura Atsuo⁹^ORCID,Florea Liliana D⁴,Savonenko Alena¹⁰,Xiao Meifang¹¹,Wu Dan¹²,Batista Denise AS¹³,Yang Junhua³,Qiu Zhaozhu³,Singh Nandini¹⁴,Richtsmeier Joan T¹⁵^ORCID,Takeuchi Takashi¹⁶,Oshimura Mitsuo¹,Reeves Roger H³⁴^ORCID

Affiliation:

1. Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Yonago, Japan

2. Chromosome Engineering Research Center (CERC), Tottori University, Yonago, Japan

3. Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, United States

4. Department of Genetic Medicine, John Hopkins University School of Medicine, Baltimore, United States

5. Department of Animal Nursing Science, Yamazaki University of Animal Health Technology, Hachioji, Tokyo, Japan

6. Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

7. Department of Molecular Hematology, Tohoku University Graduate School of Medicine, Sendai, Japan

8. Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan

9. Bioresource Engineering Division, RIKEN BioResource Research Center (BRC), Tsukuba, Japan

10. Departments of Pathology and Neurology, John Hopkins University School of Medicine, Baltimore, United States

11. Department of Neuroscience, John Hopkins University School of Medicine, Baltimore, United States

12. Department of Biomedical Engineering, Zhejiang University, Hangzhou, China

13. Department of Pathology, John Hopkins University School of Medicine, Baltimore, United States

14. Department of Anthropology, Penn State University, State College, United States

15. Division of Biosignaling, School of Life Sciences, Faculty of Medicine, Tottori University, Yonago, Japan

16. Department of Anthropology, California State University, Sacramento, United States

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.

Funder

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Japan Society for the Promotion of Science

Core Research for Evolutional Science and Technology

Publisher

eLife Sciences Publications, Ltd

Subject

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

Link

https://cdn.elifesciences.org/articles/56223/elife-56223-v3.pdf

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