Analysis of OXT function in glial cells in the pathology of Autism spectrum disorder
| Project/Area Number |
18K15508
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 52030:Psychiatry-related
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
Hiraoka Yuichi 東京医科歯科大学, 難治疾患研究所, 助教 (00778681)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | CRISPR/Cas13 / オキシトシン / アストロサイト / Cas13 / 発達障害 / 自閉症スペクトラム障害 / グリア連関 / 受容体 |
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| Outline of Final Research Achievements |
Autism spectrum disorder (ASD) is a common neurodevelopmental disorder but no effective cures has been identified. Recent studies have shown amelioration of ASD symptoms by intranasal administration of oxytocin(OXT) and demonstrated the association of polymorphisms in the oxytocin receptor (Oxtr) gene with ASD patients. In this back ground, many researchers are focusing on OXT in ASD pathology with OXT receptor (OXTR) on neurons but few are focused on glial cells. I this study, I purposed to establish novel model animal which focused on the relationship between OXT and glial cells in ASD.
ASD is a kind of developmental disorder but OXT has various functions through the lifespan. To exclude the effects not related to developmental stage, Oxtr expression must be regulated in spatio-temporal manner. CRISPR/Cas13 system was utilized to solve this problem, and OXTR expression was successfully suppressed in vitro but not in vivo.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では当初目標とした自閉症スペクトラム障害病態の解明には至らなかったが、その過程で新規な技術の開発に成功した。CRISPR/Cas13システムは、ゲノム情報を改変せずに遺伝子発現制御が可能な技術であり、現在利用されている遺伝子治療技術と比較してより安全な治療法の基礎となりうる技術である。また、新規に開発されたカルシウムシグナル阻害マウスは、オキシトシン受容体に限らず多くのGタンパク質共役型受容体研究に応用が可能である。Gタンパク質共役型受容体は昨今多くの疾患において注目される創薬標的であり、本計画で作出されたモデルマウスが今後の新規治療法開発の場において利用されることが期待される。
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Report
(3 results)
Research Products
(2 results)
