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https://hdl.handle.net/20.500.14094/90004889
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2024-04-19
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90004889 (fulltext)
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メタデータID
90004889
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open access
出版タイプ
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タイトル
Comprehensive behavioral analysis of mice deficient in Rapgef2 and Rapgef6, a subfamily of guanine nucleotide exchange factors for Rap small GTPases possessing the Ras/Rap-associating domain
著者
Maeta, Kazuhiro ; Hattori, Satoko ; Ikutomo, Junji ; Edamatsu, Hironori ; Bilasy, Shymaa E. ; Miyakawa, Tsuyoshi ; Kataoka, Tohru
著者名
Maeta, Kazuhiro
著者名
Hattori, Satoko
著者名
Ikutomo, Junji
著者ID
A0775
研究者ID
1000070335438
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=162bfcbb45dfc8f4520e17560c007669
著者名
Edamatsu, Hironori
枝松, 裕紀
エダマツ, ヒロノリ
所属機関名
医学研究科
著者名
Bilasy, Shymaa E.
著者名
Miyakawa, Tsuyoshi
著者ID
A0459
研究者ID
1000040144472
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=cb00681b17ceeeeb520e17560c007669
著者名
Kataoka, Tohru
片岡, 徹
カタオカ, トオル
所属機関名
学術研究推進機構
収録物名
Molecular Brain
巻(号)
11
ページ
27-27
出版者
BioMed Central
刊行日
2018-05-10
公開日
2018-05-25
抄録
Rapgef2 and Rapgef6 define a subfamily of guanine nucleotide exchange factors for Rap small GTPases, characterized by the possession of the Ras/Rap-associating domain. Previous genomic analyses suggested their possible involvement in the etiology of schizophrenia. We recently demonstrated the development of an ectopic cortical mass (ECM), which resembles the human subcortical band heterotopia, in the dorsal telencephalon-specific Rapgef2 conditional knockout (Rapgef2-cKO) brains. Additional knockout of Rapgef6 in Rapgef2-cKO mice resulted in gross enlargement of the ECM whereas knockout of Rapgef6 alone (Rapgef6-KO) had no discernible effect on the brain morphology. Here, we performed a battery of behavioral tests to examine the effects of Rapgef2 or Rapgef6 deficiency on higher brain functions. Rapgef2-cKO mice exhibited hyperlocomotion phenotypes. They showed decreased anxiety-like behavior in the elevated plus maze and the open-field tests as well as increased depression-like behavior in the Porsolt forced swim and tail suspension tests. They also exhibited increased sociability especially in novel environments. They showed defects in cognitive function as evidenced by reduced learning ability in the Barnes circular maze test and by impaired working memory in the T maze tests. In contrast, although Rapgef6 and Rapgef2 share similarities in biochemical roles, Rapgef6-KO mice exhibited mild behavioral abnormalities detected with a number of behavioral tests, such as hyperlocomotion phenotype in the open-field test and the social interaction test with a novel environment and working-memory defects in the T-maze test. In conclusion, although there were differences in their brain morphology and the magnitude of the behavioral abnormalities, Rapgef2-cKO mice and Rapgef6-KO mice exhibited hyperlocomotion phenotype and working-memory defect, both of which could be recognized as schizophrenia-like behavior.
キーワード
Rap small GTPases
Guanine nucleotide exchange factors
Rapgef2
Rapgef6
Behavioral analysis
Schizophrenia
カテゴリ
医学研究科
学術研究推進機構
学術雑誌論文
権利
© The Author(s). 2018
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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資源タイプ
journal article
言語
English (英語)
eISSN
1756-6606
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関連情報
DOI
https://doi.org/10.1186/s13041-018-0370-y
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