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2023 Fiscal Year Final Research Report

Pathophysiology of demyelinating diseases and epilepsy using microglia removal model by TRECK system

Research Project

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Project/Area Number 19K08311
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

SAKUMA Hiroshi  公益財団法人東京都医学総合研究所, 脳・神経科学研究分野, プロジェクトリーダー (50425683)

Project Period (FY) 2019-04-01 – 2024-03-31
Keywordsミクログリア / アストロサイト / ジフテリア毒素受容体 / TRECK法
Outline of Final Research Achievements

Using knock-in mice for tissue-specific expression of the diphtheria toxin receptor (DTR-KI), we attempted to selectively eliminate microglia or astrocytes by administration of diphtheria toxin (DT). Although microglia were selectively eliminated by DT in vitro, DT administration did not produce expected changes in tissue-specific DTR-KI mice (in which CX3CR1-CreERT2 or GFAP-Cre mice were crossed with DTR-KI mice) in vivo, suggesting that for some reason the genetic recombination was not occurring in glial cells. We also validated the experimental autoimmune encephalomyelitis and pilocarpine-induced status epilepticus models.

Free Research Field

小児神経学

Academic Significance and Societal Importance of the Research Achievements

ジフテリア毒素受容体を用いるTRECK法ではDT投与後1-2日という極めて短時間で標的細胞を除去することができる。病相特異的なグリア細胞の役割を明らかにするためには目的の時期に合わせて迅速かつ確実に除去する必要があるので、速効性というTRECK法の長所は大きな強みとなる。また組織特異的Creマウスを用いることで様々な組織の研究に幅広く応用が可能であり、疾患動物モデルと組み合わせることで特定の細胞が疾患において果たす役割を包括的に解析することができる。

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Published: 2025-01-30  

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