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

c型凝集素样受体2 （clc -2）是一种新型的血小板活化受体。我们正试图阐明CLEC-2的生理作用和信号传导机制。CARD-9是一种接头蛋白，在另一种c型凝集素样受体dectin-1的下游信号传导中起作用。在缺少CARD-9的情况下，clc -2特异性激动剂红丝胞素诱导的血小板聚集不会发生改变，这表明CARD-9不参与clc -2下游的信号传导机制。尽管我们已经成功地培育出了CLEC-2缺陷小鼠，但它们几乎是胚胎致死的。由于一些CLEC-2缺失的胎儿在E15左右可以存活，我们进一步将CLEC-2缺失的胎儿的肝细胞移植到受体小鼠身上，照射杀死骨髓中的造血干细胞，并制造出具有CLEC-2缺失血细胞（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缺陷的血液，我们可以用这些小鼠来研究CLEC-2的生理作用。接下来，我们将从嵌合体小鼠中分离骨髓巨核细胞，并试图确定CLEC-2在巨核生成和血小板产生中的作用。

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.