构建具有高水平人红细胞组成的人源化小鼠模型

项目名称： 构建具有高水平人红细胞组成的人源化小鼠模型

项目编号： No.81200397

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 胡正

作者单位： 吉林大学

项目金额： 23万元

中文摘要： 人源化小鼠模型由于在转化医学上巨大的应用前景受到越来越多的关注，但是现有模型没有成熟人红细胞的发育，严重限制了该模型在研究人红细胞发育、功能及相关疾病中的应用。我们近期研究发现，虽然小鼠巨噬细胞对人白细胞耐受，但会对人红细胞产生急性排斥，而小鼠补体在该排斥过程中可能具有重要作用。Clodronate是当前广泛使用的巨噬细胞清除剂，Clodronate 处理后的人源化小鼠的外周血中会出现成熟人红细胞，这说明小鼠巨噬细胞介导的排斥是限制人红细胞发育的直接原因。然而，由于clodronate对于免疫缺陷小鼠毒性巨大，使用后人源化小鼠大量死亡。该课题目的是建立具有稳定、高水平人红细胞组成的人源化小鼠模型，探索补体在小鼠巨噬细胞对人红细胞的一种排斥中的机制，为在活体条件下研究人红细胞的生理学和疾病问题提供有力支撑。该项研究紧扣国际研究前沿，具有较为重要的现实意义。

中文关键词： 红细胞；免疫缺陷小鼠；巨噬细胞；补体；

英文摘要： As a powerful model with the high expectation for translational medicine, more and more attention is attracted to humanized mice. However, the deficiency of mature human RBC(red blood cell) reconstitution in those animals restrain their application in the studies of human RBC development, function and relevant diseases. Recently, we found that although mouse macrophages are tolerant to human white blood cells, they mediate rapid rejection for human RBCs, in which mouse complements may play a crucial role. Clodronate is a widely used reagent for macrophage depletion in mouse. Once after clodronate treatment, mature human RBCs can be detected in the peripheral blood of humanized mice which indicate the rejection by mouse macrophage is the direct reason for the deficiency of mature human RBC reconstitution in humanized mice. While we also found that clodronate is very toxic for immunodeficient mice which lead to high death rate for humanized mice after clodronate treatment. The aim of this project is to establish a humanized mouse model with high level of human red blood cell stable reconstitution and to study the role of mouse complements in the process of human RBC rejection mediated by mouse macrophages. The outcome of our project may provide a powerful support for both human RBC physiology and pathology in vivo

英文关键词： Red blood cells；immunodeficient mouse；macrophage；complement；