2021 Fiscal Year Final Research Report
Endosomal recycling disorders: a novel disease entity caused by endosomal recycling defects
| Project/Area Number |
20K21583
|
|---|
| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Medium-sized Section 52:General internal medicine and related fields
|
|---|
| Research Institution | Nagoya City University |
|---|
Principal Investigator |
Saitoh Shinji 名古屋市立大学, 医薬学総合研究院(医学), 教授 (00281824)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
大石 久史 名古屋市立大学, 医薬学総合研究院(医学), 教授 (30375513)
|
|---|
| Project Period (FY) |
2020-07-30 – 2022-03-31
|
| Keywords | エンドソームリサイクル / 膜蛋白 |
|---|
| Outline of Final Research Achievements |
We have identified three new cases of VPS35L-related Ritscher-Schinzel syndrome (RSS), one Japanese, one French, and one Dutch case, and delineated clinical features. This is the largest collection of patients with VPS35L-related RSS, and now we have established the new clinical entity of VPS35L-related RSS. Regarding Schaaf-Yang syndrome (SYS), we have collected detailed clinical information from 25 Japanese patients with genetically confirmed SYS.
We also successfully established tissue specific conditional knock-out mice (central nervous system and mesenchymal stem cell), and recapitulate clinical features of VPS35L-related RSS. Using the mouse models, we successfully identified altered expression of membrane integral proteins.
|
| Free Research Field |
小児科学、遺伝学
|
| Academic Significance and Societal Importance of the Research Achievements |
膜蛋白のリサイクルに必須な分子機構であるエンドソームリサイクルを担うretromerおよびretriever複合体の機能障害により先天性疾患が発症することを明らかにし、エンドソームリサイクル病の疾患概念を提唱した。新しい生物学的機構の障害による疾患の存在を明らかにしたことで、エンドソームリサイクルに注目した病態解明および治療法開発のパラダイムが広がることが期待される。さらに、モデル動物を作成したことで、疾患研究の基盤を作ることができた。
|
