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The novel platelet activation receptor CLEC-2: The role of CLEC-2 for megakaryopoiesis, platelet production and its signaling mechanism

新型血小板活化受体CLEC-2：CLEC-2在巨核细胞生成、血小板生成中的作用及其信号机制

基本信息

批准号：
20790671
负责人：
INOUE Osamu
金额：
$ 2.75万
依托单位：
University of Yamanashi
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2009
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20790671/
关键词：
血栓止血学 CLEC-2 医学血栓止血血小板 CARD9

项目摘要

C-type lectin like receptor 2 (CLEC-2) is a novel platelet activating receptor. We are trying to elucidate the physiological role and signaling mechanism of CLEC-2. CARD-9 is an adaptor protein that plays a role in signalling downstream of another C-type lectin like receptor dectin-1. The platelet aggregation induced by a CLEC-2 specific agonist rhodocytin was not altered in the absence of CARD-9, suggesting that CARD-9 is not involved in the signaling mechanism downstream of CLEC-2. Although we have successfully generated CLEC-2 deficient mice, they were almost embryonic lethal. Since some of CLEC-2 null fetus can survive around E15, we further performed transplantation of liver cells of CLEC-2 null fetus to recipient mice that were irradiated to kill the hematopoietic stem cells in the bone marrow, and made chimera mice that have CLEC-2 deficient blood cells including platelets. Our CLEC-2 chimera mice successfully produce CLEC-2 deficient blood and we can investigate the physiological role of CLEC-2 using these mice. We are going to isolate bone marrow megakaryocytes from the chimera mice next and try to identify the role of CLEC-2 in megakaryopoiesis and platelet production.

C型凝集素样受体2（CLEC-2）是一种新型的血小板活化受体。我们试图阐明CLEC-2的生理作用和信号转导机制。CARD-9是一种衔接蛋白，在另一种C型凝集素样受体dectin-1的下游信号传导中发挥作用。在不存在CARD-9的情况下，由CLEC-2特异性激动剂红细胞素诱导的血小板聚集没有改变，表明CARD-9不参与CLEC-2下游的信号传导机制。虽然我们已经成功地产生了CLEC-2缺陷小鼠，但它们几乎是胚胎致死的。由于部分CLEC-2缺失胎儿在E15左右可以存活，我们进一步将CLEC-2缺失胎儿的肝细胞移植到接受辐射以杀死骨髓中的造血干细胞的受体小鼠中，并制备具有CLEC-2缺陷血细胞（包括血小板）的嵌合体小鼠。我们的CLEC-2嵌合体小鼠成功地产生了CLEC-2缺陷型血液，我们可以使用这些小鼠研究CLEC-2的生理作用。我们接下来将从嵌合体小鼠中分离骨髓巨核细胞，并试图确定CLEC-2在巨核细胞生成和血小板生成中的作用。