2021 Fiscal Year Final Research Report
Establishment of new ADHD model mice based on ganglioside deficiency
| Project/Area Number |
19K06468
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 42040:Laboratory animal science-related
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| Research Institution | Kyoto University |
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Principal Investigator |
Yoshihara Toru 京都大学, 医学研究科, 特定講師 (00401935)
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| Co-Investigator(Kenkyū-buntansha) |
浅野 雅秀 京都大学, 医学研究科, 教授 (50251450)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 行動解析 / マウス / 発達障害 / ADHD |
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| Outline of Final Research Achievements |
Gangliosides, which are synthesized from ceramide, are major molecules accounting for about 1/3 of glycolipids in the brain and are essential for the maturation of neurons. We found that β4-galactosyltransferases 5 and 6 are essential for the synthesis of lactosylceramide, the starting site of ganglioside formation, in the mouse brain by analysis of mice lacking the two enzymes in the whole brain (Yoshihara et al., 2018). Furthermore, to evaluate the behavioral properties of gangliosides in the brain, we generated mice lacking gangliosides specifically in the telencephalon and found that these mice could serve as a model for developmental disorders such as ADHD, including increased activity, motility, attention, and fear conditioning.
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| Free Research Field |
神経科学
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| Academic Significance and Societal Importance of the Research Achievements |
社会的にも大きな問題となっている発達障害に関して，様々なモデルマウスを用いた研究がなされている．申請者はガングリオシドと呼ばれる糖脂質と発達障害との関連を明らかにすることを企図して，それらの合成の起点部となるラクトシルセラミド合成に必須である2つの糖転移酵素を大脳皮質等で欠損させたマウスを作出した．このマウスの行動様式はADHD等の発達障害モデルたり得ることを見いだし，その原因や既知のモデルマウスとの比較により，新たなADHDモデルマウスを作出することができた．．これらの知見は，新たなモデルマウスによる病態理解や治療戦略に向けて，学術的，社会的意義を持つものである．
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