The analysis of biological defects of Autism by using autism mouse model.

• Project/Area Number: 16K10250
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Ritsumeikan University (2019); Shiga University of Medical Science (2016)
• Principal Investigator: Jin Nakatani 立命館大学, 生命科学部, 講師 (00342717)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 自閉症 / 疾患モデルマウス / 体重減少 / 肥満 / ADHD / 社会性行動試験 / 発達障害 / 脳神経疾患 / 行動学 / 遺伝学

Outline of Final Research Achievements

Autism Spectrum Disorder (ASD) is a pervasive developmental disorder defined by social and communication problems and emotional behavior. The etiology of the disease is unknown, even though there are various theories. In order to elucidate the biological pathogenesis of ASD, we developed a mouse model of ASD with the same genetic abnormalities as those frequently seen in human ASD patients, and examined the biological abnormalities. It turns out that this ASD mouse model has a serious developmental ploblems that causes more than 90 percent of its offspring to die shortly after birth. The few individuals that survived were able to reach adulthood despite their low growth, but at the same time they showed ADHD-like behaviors.

Academic Significance and Societal Importance of the Research Achievements

本研究によりASDモデルマウスは発生学的に重篤な致死性を示し、９割以上の子供が途中で死んだ。この様に高い致死性を示すASDモデル動物はあまり報告がなく、ASDの生物学的異常を考える上で貴重なモデルであると言うことが可能である。また少数の生き延びたモデルであっても、注意欠陥、多動性障害(ADHD)様の行動を示した。ASDモデルで多動を示す様なモデルはあまりなく、ヒトADHDの病態を考える上で重要である、と考えられる。

Research Products

• [Journal Article] Prenatal β-catenin/Brn2/Tbr2 transcriptional cascade regulates adult social and stereotypic behaviors. (2016)
  • Author(s): Belinson H, Nakatani J, Babineau BA, Birnbaum RY, Ellegood J, Bershteyn M, McEvilly RJ, Long JM, Willert K, Klein OD, Ahituv N, Lerch JP, Rosenfeld MG, Wynshaw-Boris A.
  • Journal Title: Mol Psychiatry. Volume: 21 Issue: 10 Pages: 1417-1433
  • DOI: 10.1038/mp.2015.207
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Autism model mice that have 15q11-13 chromosomal duplication shows severe developmental abnormalities. (2016)
  • Author(s): Nakatani Jin, Koyama Natsu, Hitoshi Seiji, Takumi Toru, Kato Tomoko, Tooyama Ikuo, Shiino Akihiko, Morikawa Shigehiro, Inubushi Toshiro
  • Organizer: 日本神経科学会
  • Place of Presentation: パシフィコ横浜