Generation of human urate metabolism complete model mice by suppressing xanthine dehydrogenase expression
| Project/Area Number |
17K08605
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
General pharmacology
|
|---|
| Research Institution | Teikyo University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
富岡 直子 帝京大学, 薬学部, 講師 (60525814)
金子 希代子 帝京大学, 薬学部, 教授 (90147075)
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
|---|
| Keywords | キサンチンオキシドレダクターゼ / ウリカーゼ / ヒポキサンチンホスホリボシルトランスフェラーゼ / 酵素 / 核酸 |
|---|
| Outline of Final Research Achievements |
We tried to create human urate metabolism complete model mice by uricase (Uox) deletion, hypoxanthine phosphoribosyl transferase (HPRT) high activity, and suppression of xanthine oxidoreductase (XOR) expression.
As a result, two strains of HPRT highly active Uox-Xor-double knockout mouse-human XOR transgenic mice having different human XOR expression levels were obtained. Although urinary hypoxanthine and xanthine excretion remained in both strains and blood creatinine was elevated and showed renal damage in a strain with low human XOR activity, but in a strain with high human XOR activity, blood creatinine was not elevated, In summary, human uric acid metabolism complete model mice that do not cause renal damage were obtained.
|
| Academic Significance and Societal Importance of the Research Achievements |
学術的意義は3つの遺伝子発現をヒト化することによりプリン代謝の分野で初めてヒトの病態を反映する疾患モデル動物が得られた点である。社会的意義は、(1)環境要因に伴う高尿酸血症の発症メカニズム解明が可能となり、生活習慣病の新薬開発に繋がる。(2) 家族性若年性高尿酸性血症性腎症や腎性低尿酸血症のモデルマウスの作出により、治療法の無い尿酸関連遺伝性疾患の治療薬開発に結びつく。(3)すべての研究用マウスはHPRT低活性でレッシュ=ナイハン症候群様であることから、高次脳機能の研究のためにHPRT高活性ヒトXDH低発現マウスが有用となる。
|
Report
(4 results)
Research Products
(15 results)
