A mouse model of Timothy syndrome exhibits altered social competitive dominance and inhibitory neuron development

Shin ichiro Horigane, Yukihiro Ozawa, Jun Zhang, Hiroe Todoroki, Pan Miao, Asahi Haijima, Yuchio Yanagawa, Shuhei Ueda, Shigeo Nakamura, Masaki Kakeyama, Sayaka Takemoto-Kimura

研究成果: Article査読

2 被引用数 (Scopus)

抄録

Multiple genetic factors related to autism spectrum disorder (ASD) have been identified, but the biological mechanisms remain obscure. Timothy syndrome (TS), associated with syndromic ASD, is caused by a gain-of-function mutation, G406R, in the pore-forming subunit of L-type Ca2+ channels, Cav1.2. In this study, a mouse model of TS, TS2-neo, was used to enhance behavioral phenotyping and to identify developmental anomalies in inhibitory neurons. Using the IntelliCage, which enables sequential behavioral tasks without human handling and mouse isolation stress, high social competitive dominance was observed in TS2-neo mice. Furthermore, histological analysis demonstrated inhibitory neuronal abnormalities in the neocortex, including an excess of smaller-sized inhibitory presynaptic terminals in the somatosensory cortex of young adolescent mice and higher numbers of migrating inhibitory neurons from the medial ganglionic eminence during embryonic development. In contrast, no obvious changes in excitatory synaptic terminals were found. These novel neural abnormalities in inhibitory neurons of TS2-neo mice may result in a disturbed excitatory/inhibitory (E/I) balance, a key feature underlying ASD.

本文言語English
ページ(範囲)1436-1446
ページ数11
ジャーナルFEBS Open Bio
10
8
DOI
出版ステータスPublished - 2020 8 1

ASJC Scopus subject areas

  • 生化学、遺伝学、分子生物学(全般)

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