| Project/Area Number |
18390251
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Kumamoto University |
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Principal Investigator |
NISHINAKAMURA Ryuichi Kumamoto University, Institute of Molecular Embryology and Genetics, Professor (70291309)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Chiyoko Kumamoto University, Institute of Molecular Embryology and Genetics, Assistant Professor (20342785)
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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 |
¥16,740,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2007: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2006: ¥7,900,000 (Direct Cost: ¥7,900,000)
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| Keywords | kidney development / Cre recombinase / ES cells / glomerulus / 腎臓発生 |
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| Research Abstract |
This project aims at controlling cell fates of the developing kidney, by utilizing genetic engineering and the knowledge of developmental biology. The metanephric mesenchyme gives rise to epithelia of multiple tissues including glomeruli, proximal and distal renal tubules, thus contains multipotent progenitors. The progenitors epithelialize upon Wnt stimulation and subsequently Notch2 plays an important role for establishment of the proximal fate, which includes glomerular podocytes and proximal tubules. If we can manipulate the cells fate decision of the progenitors and make the desired cell lineages as we wish, it would be beneficial for future cell therapy of the kidney. To approach to this end, we generated two lines of mice: one expressing a Cre recombinase only in the kidney mesenchymal progenitors and the other harboring stop sequences flanked by loxP sites (Cre targets) followed by the intracellular domain of Notch2, the constitutively active form. We generated the latter by using homologous recombination into the ROSA26 locus of the embryonic stem cells. When these two lines of mice were crossed, the stop sequences were excised out and Notch2 was activated in the progenitors of the kidney. Indeed all the double heterozygotes died shortly after birth and the kidney size was reduced remarkably. We have preliminary data indicating that the progenitors were prematurely depleted by the activation of Notch2, and need to confirm it with immunostaining and other methods. By using the mice, we plan to develop eventually a method to induce the progenitors toward the glomeruli and other lineages, which would help regenerate the kidney.
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