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A mouse model of Timothy syndrome exhibits altered social competitive dominance and inhibitory neuron development
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 Ca(2+) channels, Ca(v)1....
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396430/ https://www.ncbi.nlm.nih.gov/pubmed/32598571 http://dx.doi.org/10.1002/2211-5463.12924 |
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author | Horigane, Shin‐ichiro Ozawa, Yukihiro Zhang, Jun Todoroki, Hiroe Miao, Pan Haijima, Asahi Yanagawa, Yuchio Ueda, Shuhei Nakamura, Shigeo Kakeyama, Masaki Takemoto‐Kimura, Sayaka |
author_facet | Horigane, Shin‐ichiro Ozawa, Yukihiro Zhang, Jun Todoroki, Hiroe Miao, Pan Haijima, Asahi Yanagawa, Yuchio Ueda, Shuhei Nakamura, Shigeo Kakeyama, Masaki Takemoto‐Kimura, Sayaka |
author_sort | Horigane, Shin‐ichiro |
collection | PubMed |
description | 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 Ca(2+) channels, Ca(v)1.2. 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. |
format | Online Article Text |
id | pubmed-7396430 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-73964302020-08-06 A mouse model of Timothy syndrome exhibits altered social competitive dominance and inhibitory neuron development Horigane, Shin‐ichiro Ozawa, Yukihiro Zhang, Jun Todoroki, Hiroe Miao, Pan Haijima, Asahi Yanagawa, Yuchio Ueda, Shuhei Nakamura, Shigeo Kakeyama, Masaki Takemoto‐Kimura, Sayaka FEBS Open Bio Research Articles 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 Ca(2+) channels, Ca(v)1.2. 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. John Wiley and Sons Inc. 2020-07-19 /pmc/articles/PMC7396430/ /pubmed/32598571 http://dx.doi.org/10.1002/2211-5463.12924 Text en © 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Horigane, Shin‐ichiro Ozawa, Yukihiro Zhang, Jun Todoroki, Hiroe Miao, Pan Haijima, Asahi Yanagawa, Yuchio Ueda, Shuhei Nakamura, Shigeo Kakeyama, Masaki Takemoto‐Kimura, Sayaka A mouse model of Timothy syndrome exhibits altered social competitive dominance and inhibitory neuron development |
title | A mouse model of Timothy syndrome exhibits altered social competitive dominance and inhibitory neuron development |
title_full | A mouse model of Timothy syndrome exhibits altered social competitive dominance and inhibitory neuron development |
title_fullStr | A mouse model of Timothy syndrome exhibits altered social competitive dominance and inhibitory neuron development |
title_full_unstemmed | A mouse model of Timothy syndrome exhibits altered social competitive dominance and inhibitory neuron development |
title_short | A mouse model of Timothy syndrome exhibits altered social competitive dominance and inhibitory neuron development |
title_sort | mouse model of timothy syndrome exhibits altered social competitive dominance and inhibitory neuron development |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396430/ https://www.ncbi.nlm.nih.gov/pubmed/32598571 http://dx.doi.org/10.1002/2211-5463.12924 |
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