• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Establishment of animal models for pharmaceutical experiment in polycystic kidney disease (PKD)

Research Project

Project/Area Number 18590876
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionHokkaido University

Principal Investigator

MOCHIZUKI Toshio  Hokkaido University, Hokkaido University Hospital, Assistant Professor (00277120)

Co-Investigator(Kenkyū-buntansha) WAKAMATSU Yuko  Nagoya Univ, Bioscience and Biotechnology Center, Professor (20026800)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,920,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsPolycystic kidney / ADPKD / PKD1 / PKD2 / Pkd1 knockout mouse / Teromerase deficient mouse / tansgenic medaka
Research Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is a most common human hereditary renal disease mutated in either PKD1 or PKD2 gene. We planned to generate animal models for pharmaceutical experiment in polycystic kidney disease using mice and small fish, medaka.
First, Pkd1 knockout hetero mice (Pkd1^<+/->) were intercrossed with telomerase-deficiency mice. Telomere shortening could lead frequent somatic mutation because of genome instability. Although early cystogenesis seemed to be indicated in Pkd1^<+/->/Terc^<+/-> (homo) mice compared to Pkd1^<+/->/Terc^<+/-> (hetero) mice, polycystic kidneys like human ADPKD were not generated in our experiment.
Second, we generated transgenic medaka carrying a deletion mutant of medaka Pkd2 cDNA. Beside the transgenic strain with EF-1α promotor (EF-1α-A-EGFP-pkd2ΔC) strains, other strain (Tet-On EGFP-pkd2ΔC strain) was obtained by mating one strain of transcriptional factor rtTA (EF-1α-A-tTA) and one strain of the deletion mutant of medaka Pkd2 gene with Tet-on vector. Various number of cysts were observed in the kidneys of EF-1α promotor strains. Furthermore, Tet-On strains after four months revealed polycystic kidneys resembled to human ADPKD. These results suggest that a deletion mutant of medaka Pkd2 gene inhibit intrinsic Pkd2 gene in a dominant-negative manner. In the future, we hope that this transgenic medaka could be an animal model for pharmaceutical experiment in polycystic kidney disease.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (2 results)

All 2008

All Journal Article (2 results) (of which Peer Reviewed: 1 results)

  • [Journal Article] 常染色体優性多発性嚢胞腎モデルメダカの作成と解析2008

    • Author(s)
      宮本 兼玄
    • Journal Title

      北海道医学雑誌 83

      Pages: 103-114

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Generation and analysis of transgenic medaka as a disease model for autosomal dominant polycystic kidney disease (ADPKD).2008

    • Author(s)
      Tomotsune Miyamoto
    • Journal Title

      The Hokkaido Journal of Medical Science 83,2

      Pages: 103-114

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

URL: 

Published: 2006-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi