Establishment of animal models for pharmaceutical experiment in polycystic kidney disease (PKD)
| Project/Area Number |
18590876
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Hokkaido University |
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Principal Investigator |
MOCHIZUKI Toshio Hokkaido University, Hokkaido University Hospital, Assistant Professor (00277120)
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| Co-Investigator(Kenkyū-buntansha) |
WAKAMATSU Yuko Nagoya Univ, Bioscience and Biotechnology Center, Professor (20026800)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| 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)
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| Keywords | Polycystic kidney / ADPKD / PKD1 / PKD2 / Pkd1 knockout mouse / Teromerase deficient mouse / tansgenic medaka |
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| 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.
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Report
(3 results)
Research Products
(2 results)
