The exploratory research of congenital hydronephrosis using animal model

• Project/Area Number: 15K10631
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Jichi Medical University
• Principal Investigator: Takayama Tatsuya 自治医科大学, 医学部, 准教授 (90324350)
• Co-Investigator(Kenkyū-buntansha): 森田 辰男 自治医科大学, 医学部, 教授 (40200422) ; 中井 秀郎 自治医科大学, 医学部, 教授 (50167540) ; 久保 太郎 自治医科大学, 医学部, 助教 (50508744) ; 寺谷 工 自治医科大学, 医学部, 講師 (70373404)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
• Keywords: 先天性水腎症 / ポリアミン / 水腎症モデル動物 / ゲノムDNA解析

Outline of Final Research Achievements

The phenomenon that hydronephrosis developed when Luciferase-Transgenic LEW rats were fed with an appropriate amount of polyamine, and hydronephrosis recovered by stopping intake of polyamine was confirmed. It has been suggested that the polyamine-responsive gene cluster is deeply involved in the onset of hydronephrosis and that it is very promising as a pediatric congenital hydronephrosis animal model. Furthermore, induced hydronephrosis is not a direct cause of polyamine intake, but a mutation on a chromosome is a direct factor, suggesting the involvement of a polyamine. Genomic DNA is extracted for the purpose of searching gene regions and gene groups involved in the onset mechanism of hydronephrosis caused by polyamine intake, and the base sequence is determined.

Academic Significance and Societal Importance of the Research Achievements

先天性水腎症発症機序に関わる遺伝子領域および遺伝子群が同定されることにより、先天性水腎症に対する新しい治療ストラテジーを提供すると同時に、発生学の新しい道筋を見出す可能性があり学術的意義は大きい。また、対象患者の病態が経過観察で良いか、それとも外科的治療が必要なのかを選別できる指標を探索することも可能となり、対象患者の精神的および肉体的苦痛を軽減し、患者のQOL の向上も期待でき、社会的意義も期待できる。