| Project/Area Number |
16590777
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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 | Kumamoto University |
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Principal Investigator |
NISHINAKAMURA Ryuichi Kumamoto University, Institute of Molecular Embryology and Genetics, Professor, 発生医学研究センター, 教授 (70291309)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Sall1 / kidney development / knockout mouse / podocyte / glomerulus / podocyte / 腎臓 |
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| Research Abstract |
Sall is a zinc finger protein which is conserved from Drosophila to humans. We previously found that mice deficient in Sall1 lack kidney and that Sall1 is essential for the initial stage of kidney development. We also found that Sall1 is expressed not only in the metanephric mesenchyme but also in glomerular podocytes. Podocytes are derived from the mesenchyme and functions as a filter barrier from the blood stream to the urine. This study aims to reveal Sall1 functions in podocytes, by generating podocyte-specific Sall1-deficient mice. We generated embryonic stem (ES) cells which contain a modified exon 1 of Sall1, by using homologous recombination. The exon 1 was flanked by lox P sites, which are targets of Cre recombinase. The ES cells were used to generate chimeric mice and eventually heterozygous mice (floxed mice). Homozygous floxed mice were healthy, indicating that these mice retain normal Sall1 functions before Cre excision. When flox mice were crossed with mice expressing Cre ubiquitously, they lacked the kidney, which is consistent with the phenotypes of the conventional Sall1-deficient mice. Floxed mice were then crossed with podocin-Cre or nephrin-Cre mice, both of which express Cre under the promoters of podocyte-specific genes (podocin and nephrin). However, the podocyte-specific Sall1-deficient mice showed no abnormalities in renal functions or in kidney structure including podocytes. Thus Sall1 is not essential for the development of the podocytes.
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