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開催日 2014/9/12
時間 14:00 - 15:00
会場 Poster / Exhibition(Event Hall B)

Comprehensive behavioral analysis of forebrain- and dentate gyrus-specific Schnurri-2 knockout mice

  • P2-324
  • 服部 聡子 / Satoko Hattori:1,2 高雄 啓三 / Keizo Takao:2,3 山崎 真弥 / Maya Yamazaki:4 遠山 桂子 / Keiko Toyama:1,2 梅森 十三 / Juzoh Umemori:1,2 崎村 建司 / Kenji Sakimura:4 宮川 剛 / Tsuyoshi Miyakawa:1,2,3 
  • 1:藤田保健衛生大 総合医科学研究所 システム医科学 / Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Aichi, Japan 2:JST, CREST / JST, CREST, Japan 3:生理学研究所 行動・代謝分子解析センター 行動様式 / Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Aichi, Japan 4:新潟大 脳研究所 細胞神経生物学 / Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan 

Schnurri-2 (Shn-2; also called MBP-2, Hivep2 or Mibp1) was originally identified as a nuclear factor- κB site-binding protein, and is expressed in several brain regions, such as hippocampus, cortex, and cerebellum. It tightly binds to the enhancers of major histocompatibility complex genes and inflammatory cytokines, which have been shown to associate with schizophrenia. In previous study, we reported that Shn-2 conventional knockout (Shn-2 KO) mice exhibited hyperactivity and cognitive impairment that resemble symptoms in human patients with schizophrenia. The mutant brain also demonstrated multiple schizophrenia-related phenotypes, including the "immature dentate gyrus " phenotype, which has been proposed as a common phenomenon in the animal model and patient of the psychiatric disorders. In this study, we conditionally knocked out Shn-2 in the forebrain or dentate gyrus by using Cre/loxp technology, and the two different strains of conditional Shn-2 KO mice were subjected to a comprehensive behavioral test battery. Forebrain-specific Shn-2 KO mice showed increased locomotor activity in the open field test and decreased correct responses in T-maze spontaneous alternation task. In the Barnes Maze test, dentate gyrus-specific Shn-2 KO mice exhibited increased time spent around target hole in probe test performed one month after the last training session, indicating impairment in remote memory. These results demonstrate distinct contribution of Shn-2 in different brain regions / cell types to schizophrenia-related behaviors, such as hyperactivity and cognitive impairment.

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