| Project/Area Number |
17380175
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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 |
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 Agriculture 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) |
KUROHMARU Masamichi The University of Tokyo, Graduate School of Agriculture and Life Sciences, Professor, 大学院農学生命科学研究科, 教授 (00148636)
TAYA Chouji The Tokyo Metropolitan Institute of Medical Science, Department of Laboratory Animal Science, Research Associate, 実験動物研究部門, 研究員 (90175456)
TAJIMA Youichi The Tokyo Metropolitan Institute of Medical Science, Department of Clinical Genetics, Research Associate, 臨床遺伝学研究部門, 研究員 (00300955)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2006: ¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 2005: ¥8,000,000 (Direct Cost: ¥8,000,000)
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| Keywords | SOX17 / SOX18 / angiogenesis / Knockout mice / animal model |
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| Research Abstract |
Sox7, -17 and -18 constitute subgroup F (SoxF) of the Sox family of HMG box transcription factor genes, which all are co-expressed in developing vascular endothelial cells in a organ/site-specific manner in mice, Redundant roles of these three SoxF members in cardiovascular development were previously demonstrated by phenotypic analyses of three spontaneous ragged (Sox18 dominant-negative) mutants and Sox17^<+/->/Sox18^<-/->-double mutant mice. In order to clarify the redundant roles of Sox17 and Sox18 in early embryonic vascular development, we here examined cardiovascular phenotypes of Sox17/Sox18-double and Sox17-single null embryos during early-somite stages (〜9.0 dpc) just before the appearance of severe posterior growth defects by the loss of endodermal actions in the Sox17 single-null embryos. Whole-mount PECAM staining has demonstrated the defects in heart morphogenesis (i.e., aberrant heart-looping and enlarged cardinal vein) in Sox17 single-null embryos from 8.5 dpc. In addition to these heart defects, the Sox17/Sox18 double-null embryos displayed defective anterior dorsal aorta formation and, in some cases, defective formation and fusion of endocardial tube at the similar stages. In contrast, the posterior dorsal aorta and allantoic microvasculatures were properly formed in the Sox17/Sox18-double null embryos. The anomalies in anterior dorsal aorta corresponded with the sites of weak Sox7 expressions in the developing vasculature, while defective heart morphogenesis in the Sox17 single-mutants is not likely associated with SoxF expression profiles. These findings, therefore, support the idea showing the region/site-specific redundant activities of three SoxF members in cardiovascular development, in addition to non-cell autonomous Sox17 roles on heart morphogenesis.
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