| Project/Area Number |
17K07757
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Applied biochemistry
|
|---|
| Research Institution | Hiroshima University |
|---|
Principal Investigator |
YANAKA Noriyuki 広島大学, 統合生命科学研究科(生), 准教授 (70346526)
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
|---|
| Keywords | choline / ゲノム編集 / GDE5 / glycerophosphocholine / コリン / グリセロホスホコリン / liver / genome editing / GPC |
|---|
| Outline of Final Research Achievements |
Choline is an essential nutrient for the de novo synthesis of cell membrane phospholipid PC, methyl donor betaine, and neurotransmitter acetylcholine. It is well-known that choline deficiency causes various diseases such as fatty liver, whereas the nutritional importance of choline is under-recognized. Here, I tried to generate GDE5 KO mouse model using CRISPR-Cas9 genome editing to show the involvement of GDE5 in choline synthesis in vivo and the nutritional importance of choline in a tissue-specific manner. In this study, I established liver-specific GDE5-deficient mice and showed that GPC was accumulated and betaine level was decreased. Also, S-adenocylmethionine, a major methyl donor, was decreased and, in contrast, S-adenocylhomocysteine was increased. This study firstly demonstrated that GDE5 has an important function in choline synthetic pathway and plays roles in methyl group metabolism in vivo.
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究では、GDE5のcholine供給に果たす役割をin vivoで初めて実証するとともに、標的組織特異的にcholine代謝を変動させ、同組織でのcholine代謝の重要性を検証する手法として利用されるものである。特に、肝臓組織特異的なcholine欠乏による肝障害を誘導するためには、choline欠乏食による長期の飼育が必要であると考えられているが、GDE5のcholine供給を遮断するマウスモデルとして利用することによって、より詳細なcholineの栄養学的重要性を提示しえるものと期待される。
|
