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Thromb Haemost 2019; 119(03): 377-383
DOI: 10.1055/s-0038-1677032
Cellular Haemostasis and Platelets
Georg Thieme Verlag KG Stuttgart · New York

Novel Murine Model of Immune Thrombocytopaenia through Immunized CD41 Knockout Mice

Xin Li
1   Department of Hematology, Qilu Hospital, Shandong University, Jinan, Shandong, China
,
Shu-wen Wang
1   Department of Hematology, Qilu Hospital, Shandong University, Jinan, Shandong, China
,
Qi Feng
1   Department of Hematology, Qilu Hospital, Shandong University, Jinan, Shandong, China
,
Yu Hou
1   Department of Hematology, Qilu Hospital, Shandong University, Jinan, Shandong, China
2   Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, Shandong, China
,
Nan Lu
3   Institute of Diagnostics, School of Medicine, Shandong University, Jinan, Shandong, China
,
Chun-hong Ma
4   Department of Immunology, Shandong University School of Medicine, Shandong University, Jinan, Shandong, China
,
Cheng-jiang Gao
4   Department of Immunology, Shandong University School of Medicine, Shandong University, Jinan, Shandong, China
,
Ming Hou
1   Department of Hematology, Qilu Hospital, Shandong University, Jinan, Shandong, China
2   Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, Shandong, China
5   Leading Research Group of Scientific Innovation, Department of Science and Technology of Shandong Province, Jinan, Shandong, China
,
Jun Peng
1   Department of Hematology, Qilu Hospital, Shandong University, Jinan, Shandong, China
2   Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, Shandong, China
› Author Affiliations Funding This work was supported by grants from the National Natural Science Foundation of China (No. 91442204, No. 81770133, No. 81370623, No. 81770114, No. 81800112, No. 81500095), Natural Science Foundation of Shandong Province (ZR2017PH022, ZR2017PH041) and Tai Shan Scholar Foundation of Shandong Province.
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Publication History

22 July 2018

28 November 2018

Publication Date:
10 January 2019 (online)

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Abstract

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.

Keywords

bleeding disorder - immune thrombocytopaenia - mouse model - CD41 - SCID mouse

Authors' Contributions

J.P. and M.H. designed the research, analysed the data and wrote the paper. X.L. performed the research, analysed the data and wrote the paper. S.-w.W, Q.F. and Y.H. performed the research and analysed the data. N.L., C.-h.M. and C.-j.G. analysed the data.


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