| Project/Area Number |
11470336
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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 |
Urology
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
KAMOTO Tsohiyuki Kyoto Univ., Graduate School of Medicine, Assistant Prof., 医学研究科, 講師 (00281098)
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| Co-Investigator(Kenkyū-buntansha) |
TERAI Akito Kyoto Univ., Graduate School of Medicine, Assistant Prof, 医学研究科, 講師 (50243019)
HIAI Hiroshi Kyoto Univ., Graduate School of Medicine, Professor, 医学研究科, 教授 (10073131)
OGAWA Osamu Kyoto Univ., Graduate School of Medicine, Professor, 医学研究科, 教授 (90260611)
NAKAMURA Eijiro Kyoto Univ., Graduate School of Medicine, Assistant Prof, 医学研究科, 助手 (90293878)
MOROI Seiji Kyoto Univ., Graduate School of Medicine, Assistant Prof, 医学研究科, 助手 (50314191)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥11,200,000 (Direct Cost: ¥11,200,000)
Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2000: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1999: ¥5,800,000 (Direct Cost: ¥5,800,000)
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| Keywords | renal agenesis / animal model / ureteric bud / metanephros / FUBI / 腎発生 / 器官培養 / 後腎 / 上皮-間質相互作用 / 上皮―間質相互作用 |
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| Research Abstract |
Organogenesis of the kidney consists of at least four steps. Step 1 is formation of the metanephric mesenchyme in the intermediate mesoderm and subsequent outgrowth of the ureteric bud from the Wolffian duct. Mutation-induced congenital anomalies are promising tools for investigating critical genetic events in organogenesis. So far several Spontaneous murine models of defects in renal organogenesis have been reported, including Danforth Short Tail (Sd), urogenital syndrome (us) and limb deformity (Id). Furthermore, genetic manipulations have identified a number of genes that affect the organogenesis of the urogenital system. Unlike the anomalies in most other models, the anomaly in FUBI mice is pure renal agenesis without accompanying urogenital or skeletal system malformations FUBI (failure of ureteric bud invasion) is a highly inbred strain of mouse with a high spontaneous incidence of uni- or bilateral renal agenesis (60%). Bilateral renal agenesis is lethal within 2 days after birt
… More
h. The primary defect of FUBI is failure of the ureteric bud to penetrate into the metanephric mesenchyme at around embryonic day 1 1, resulting in apoptosis of metanephric cells and leading to renal agenesis on the affected side. The metanephros seemed to be normal because co-culturing of the FUBI metanephros with homologous spinal cord induced differentiation of the rudiment, but co-culturing with the homologous ureteric bud frequently did not. Genetic analysis revealed that more than two genes were involved in this malformation and we mapped one of the modifier loci,fubil, on chromosome 2, at 〜65 cM from the centromere. In this region, there are two possible candidate genes, Wilms ' tumor 1 andformin, that play important roles in kidney development. Some offormin mutants shared a similar phenotype with FUBI; however, there was no difference in the expression offormin in embryonic kidneys between FUBI and control NFS/N mice. Studies offubil congenic mice indicated that interaction of two or more loci is essential for the FUBI phenotype Less
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