Novel Murine Model of Immune Thrombocytopaenia through Immunized CD41 Knockout Mice

Xin Li; Shu-wen Wang; Qi Feng; Yu Hou; Nan Lu; Chun-hong Ma; Cheng-jiang Gao; Ming Hou; Jun Peng

doi:10.1055/s-0038-1677032

Thrombosis and Haemostasis, Table of Contents

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

Authors

Xin Li

¹Department of Hematology, Qilu Hospital, Shandong University, Jinan, Shandong, China
Shu-wen Wang

¹Department of Hematology, Qilu Hospital, Shandong University, Jinan, Shandong, China
Qi Feng

¹Department of Hematology, Qilu Hospital, Shandong University, Jinan, Shandong, China
Yu Hou

¹Department of Hematology, Qilu Hospital, Shandong University, Jinan, Shandong, China

²Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, Shandong, China
Nan Lu

³Institute of Diagnostics, School of Medicine, Shandong University, Jinan, Shandong, China
Chun-hong Ma

⁴Department of Immunology, Shandong University School of Medicine, Shandong University, Jinan, Shandong, China
Cheng-jiang Gao

⁴Department of Immunology, Shandong University School of Medicine, Shandong University, Jinan, Shandong, China
Ming Hou

¹Department of Hematology, Qilu Hospital, Shandong University, Jinan, Shandong, China

²Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, Shandong, China

⁵Leading Research Group of Scientific Innovation, Department of Science and Technology of Shandong Province, Jinan, Shandong, China
Jun Peng

¹Department of Hematology, Qilu Hospital, Shandong University, Jinan, Shandong, China

²Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, Shandong, China

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

Full Text

References

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