Redundant function of Sox17 and Sox18 in mouse angiogenesis

Sox17 和 Sox18 在小鼠血管生成中的冗余功能

基本信息

批准号：
15580254
负责人：
KANAI Yoshiakira
金额：
$ 2.3万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15580254/
关键词：
Sox17 Sox18 angiogenesis liver kidney Vcam-1 gut endoderm mouse Sox07 欠陥形成

项目摘要

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.

Sry 相关的 HMG 盒转录因子基因 Sox18 是 Sox 亚组 F（Sox7、Sox17 和 Sox18）的成员，此前已被证明在小鼠和人类的正常血管发育中发挥着至关重要的作用。在这里，我们展示了 Sox17（肠道内胚层形成所必需的另一个成员）在小鼠出生后发育过程中正常血管形成中的冗余功能。为了检查Sox17和Sox18可能的冗余功能，我们生成了Sox17^<+/->/Sox18^<-/->突变小鼠，并将其与Sox17^<+/->/的表型进行比较。 Sox18^</-/-> 或 Sox17^<+/->/Sox18^<+/-> 突变小鼠。结果，Sox17^<+/+>/Sox18^<-/-> 和 Sox17^<+/->/Sox18^<+/-> 突变体都是可存活和可育的，并且不显示任何总体解剖学或物理特征。异常。相比之下，Sox17^<+/->/Sox18^<-1->突变体在 4 至 14 dpp 期间清楚地显示出有缺陷的血管生成，这很可能导致大约一半的 Sox17^<+/->/Sox18^ 出生后死亡。 </-/-> 老鼠。最早可识别的缺陷是在 4 dpp 左右肝脏和肾脏中的血管减少，这可能会在 7-14 dpp 期间促进肝肝和肾尿管上皮细胞的坏死细胞死亡。因此，这些发现强烈表明，Sox17 和 Sox18 是出生后发育中多个器官的适当血管生成共同所必需的，强调了所有三个 Sox 亚组 F 成员共同参与哺乳动物血管发育的观点。