Neocortical neuronal production and maturation defects in the TcMAC21 mouse model of Down syndrome

Nobuhiro Kurabayashi; Kazuki Fujii; Yuta Otobe; Shingo Hiroki; Masaharu Hiratsuka; Hikari Yoshitane; Yasuhiro Kazuki; Keizo Takao

iScience (Dec 2023)

Neocortical neuronal production and maturation defects in the TcMAC21 mouse model of Down syndrome

Nobuhiro Kurabayashi,
Kazuki Fujii,
Yuta Otobe,
Shingo Hiroki,
Masaharu Hiratsuka,
Hikari Yoshitane,
Yasuhiro Kazuki,
Keizo Takao

Affiliations

Nobuhiro Kurabayashi: Department of Behavioral Physiology, Faculty of Medicine, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan; Circadian Clock Project, Tokyo Metropolitan Institute of Medical Science, Kamikitazawa 2-1-6, Setagaya-ku, Tokyo 156-8506, Japan; Research Center for Idling Brain Science, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan; Corresponding author
Kazuki Fujii: Department of Behavioral Physiology, Faculty of Medicine, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan; Research Center for Idling Brain Science, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan
Yuta Otobe: Circadian Clock Project, Tokyo Metropolitan Institute of Medical Science, Kamikitazawa 2-1-6, Setagaya-ku, Tokyo 156-8506, Japan; Department of Biological Sciences, School of Science, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan
Shingo Hiroki: Circadian Clock Project, Tokyo Metropolitan Institute of Medical Science, Kamikitazawa 2-1-6, Setagaya-ku, Tokyo 156-8506, Japan
Masaharu Hiratsuka: Department of Chromosome Biomedical Engineering, School of Life Science, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan; Chromosome Engineering Research Center, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan
Hikari Yoshitane: Circadian Clock Project, Tokyo Metropolitan Institute of Medical Science, Kamikitazawa 2-1-6, Setagaya-ku, Tokyo 156-8506, Japan; Department of Biological Sciences, School of Science, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan
Yasuhiro Kazuki: Department of Chromosome Biomedical Engineering, School of Life Science, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan; Chromosome Engineering Research Center, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan; Chromosome Engineering Research Group, The Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan
Keizo Takao: Department of Behavioral Physiology, Faculty of Medicine, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan; Research Center for Idling Brain Science, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan; Corresponding author

Journal volume & issue: Vol. 26, no. 12
p. 108379

Abstract

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Summary: Down syndrome (DS) results from trisomy of human chromosome 21 (HSA21), and DS research has been conducted by the use of mouse models. We previously generated a humanized mouse model of DS, TcMAC21, which carries the long arm of HSA21. These mice exhibit learning and memory deficits, and may reproduce neurodevelopmental alterations observed in humans with DS. Here, we performed histologic studies of the TcMAC21 forebrain from embryonic to adult stages. The TcMAC21 neocortex showed reduced proliferation of neural progenitors and delayed neurogenesis. These abnormalities were associated with a smaller number of projection neurons and interneurons. Further, (phospho-)proteomic analysis of adult TcMAC21 cortex revealed alterations in the phosphorylation levels of a series of synaptic proteins. The TcMAC21 mouse model shows similar brain development abnormalities as DS, and will be a valuable model to investigate prenatal and postnatal causes of intellectual disability in humans with DS.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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