| Project/Area Number |
15580254
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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 |
Basic veterinary science/Basic zootechnical science
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KANAI Yoshiakira The University of Tokyo, Graduate School of Agricultural and Life Sciences, Associate Professor, 大学院・農学生命科学研究科, 助教授 (30260326)
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| Co-Investigator(Kenkyū-buntansha) |
YONEKAWA Hiromichi The Tokyo Metropolitan Institute of Medical Science, Vice-Director (Researcher), 実験動物研究部門, 副所長(研究職) (30142110)
HAYASHI Yoshihiro The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor, 大学院・農学生命科学研究科, 教授 (90092303)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Sox17 / Sox18 / angiogenesis / liver / kidney / Vcam-1 / gut endoderm / mouse / Sox07 / 欠陥形成 |
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| Research Abstract |
The Sry-related HMG box transcription factor gene, Sox18, a member of the Sox subgroup F (Sox7, Sox17 and Sox18), was previously shown to have a crucial role in proper vascular development in both mouse and human. Here we show a redundant function of Sox17, another member essential for gut endoderm formation, in proper vascular formation during mouse postnatal development. In order to examine a possible redundant function of Sox17 and Sox18, we have generated the Sox17^<+/->/Sox18^<-/-> mutant mice, and compared their phenotypes with those of Sox17^<+/->/Sox18^<-/-> or Sox17^<+/->/Sox18^<+/-> mutant mice. As a result, both Sox17^<+/+>/Sox18^<-/-> and Sox17^<+/->/Sox18^<+/->mutants were viable and fertile and do not display any gross anatomical or physical abnormalities. In contrast, Sox17^<+/->/Sox18^<-1->mutant clearly showed defective angiogenesis during 4 to 14 dpp, which most likely caused postnatal lethality in approximately half of the Sox17^<+/->/Sox18^<-/-> mice. The earliest recognizable defect is reduced blood vessels in the liver and kidney at around 4 dpp, which may promote necrotic cell death of both liver hepatic and kidney urinary tubule epithelial cells during 7-14 dpp. Therefore, these findings strongly indicate that Sox17 and Sox18 are jointly required for proper angiogenesis of several organs in the postnatal development, highlighting the idea that all three Sox subgroup F members are cooperatively involved in the mammalian vascular development.
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