标题：Novel Murine Model of Immune Thrombocytopaenia through Immunized CD41 Knockout Mice
作者：Li, Xin; Wang, Shu-wen; Feng, Qi; Hou, Yu; Lu, Nan; Ma, Chun-hong; Gao, Cheng-jiang; Hou, Ming; Peng, Jun
作者机构：[Li, Xin; Wang, Shu-wen; Feng, Qi; Hou, Yu; Hou, Ming; Peng, Jun] Shandong Univ, Qilu Hosp, Dept Hematol, 107 West Wenhua Rd, Jinan 250012, Shandong, 更多
通讯作者：Hou, M;Peng, J
通讯作者地址：[Hou, M; Peng, J]Shandong Univ, Qilu Hosp, Dept Hematol, 107 West Wenhua Rd, Jinan 250012, Shandong, Peoples R China.
来源：THROMBOSIS AND HAEMOSTASIS
关键词：bleeding disorder; immune thrombocytopaenia; mouse model; CD41; SCID; mouse
摘要：Immune thrombocytopaenia (ITP) is the most common autoimmune bleeding disorder, where platelets are destroyed by auto-antibodies and/or cell-mediated mechanisms. To understand the pathogenesis of ITP and explore novel therapeutics, three types of animal models have been used: passive ITP, secondary ITP and platelet-induced ITP. However, the first two are not ideal for chronic ITP pathophysiology where both T cell and B cell play important roles in platelet destruction. The most efficient model to mimic chronic ITP is developed by Chow et al through transferring splenocytes from platelet-immune CD61-knockout (KO) mice into mice with severe combined immunodeficiency (SCID). However, placental defects are evident in 25% of CD61-KO females and post-natal haemorrhage does occur, reducing the survival rate of embryos and pups. Compared with CD61-KO mice, CD41-KO ones do not present such problems. In our study, we employ CD41-KO mice as another source of immunized spleen cells. We evaluated our model with existing standards. Transferred SCID mice presented typical features of ITP, such as reduced platelet counts in the peripheral blood, increased anti-platelet antibody levels in the serum and reduced mature megakaryocytes in the bone marrow. What is more, lymphocyte-depletion experiments showed the role of CD8(+) T cells in mature megakaryocyte decrease and thrombocytopaenia. And we confirmed the antibody-mediated platelet destruction by phagocytosis in the spleen. Our study develops another efficient murine ITP model through immunized CD41-KO mice.