| Project/Area Number |
17K17605
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Obstetrics and gynecology
General medical chemistry
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2017-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Keywords | 精子エピゲノム / 神経発達障害 / 加齢 / 発生・分化 / 老化 / 発現制御 / 脳神経疾患 |
|---|
| Outline of Final Research Achievements |
In this study, we clarified the expression of REST / NRSF during the spermatogenesis process, which was unknown until now. Analysis of gene expression data in the germ cell line of the cell fractionated testis shows that REST / NRSF is most expressed in A-type spermatozoa, known as germline stem cells and the expression levels was decreased with progress of spermatogenesis. Furthermore, by creating a knock-in mouse with an epitope tag attached to the C-terminus of endogenous REST / NRSF, we have clarified for the first time the expression and localization of REST / NRSF protein in germ cell line.
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究により、雄の生殖細胞系列におけるREST/NRSFの発現と局在が初めてを明らかとなり、加齢より精子DNAメチル化異常が生じる分子機構の一端に迫ることができた。父親の高齢は子どもの自閉スペクトラム障害や統合失調症といった疾患のリスク因子であり、加齢により生じる精子DNAメチル化の変化がその原因の1つである可能性が指摘されている。今後、精子形成におけるREST/NRSFの機能を検討することにより、REST/NRSFによる精子DNAメチル化の制御機構が明らかとなれば、高齢の父親に由来する子孫の疾患リスクを低減するような予防的介入法の開発につながると期待される。
|
