Deficiency of the mouse complement regulatory protein mCd59b results in spontaneous hemolytic anemia with platelet activation and progressive male infertility
Deficiency of the mouse complement regulatory protein mCd59b results in spontaneous hemolytic anemia with platelet activation and progressive male infertility
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DOI：
10.1016/s1074-7613(03)00022-0
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发表时间：
2003-02-01
期刊：
影响因子：
32.4
通讯作者：
Halperin, JA
中科院分区：
文献类型：
--
作者：
Qin, XB;Krumrei, N;Halperin, JA
基础补体活性对受到补体调节因子（包括CD 59）严密保护的“自身”细胞存在潜在危险。小鼠表达两种Cd 59基因（mCd 59 a和mCd 59 b）; mCd 59 b比mCd 59 a高约6倍。一致地，mCd 59 b敲除小鼠呈现强表型，其特征在于溶血性贫血伴网织红细胞增加、异异形红细胞增多、棘红细胞增多、裂红细胞增多、血浆中游离血红蛋白、血红蛋白尿伴含铁血黄素尿和血小板活化。值得注意的是，mCd 59 b（-/-）雄性表达了与5个月龄后的不动畸形和更少的精子细胞相关的生育力的进行性丧失。这项工作表明mCd 59 b是小鼠中的关键补体调节因子，而CD 59对于保护自身细胞至关重要;它还为研究人类疾病中的补体调节提供了一种新模型。
Basal complement activity presents a potential danger for "self" cells that are tightly protected by complement regulators including CD59. Mice express two Cd59 genes (mCd59a and mCd59b); mCd59b has approximately a 6-fold higher specific activity than mCd59a. Consistently, mCd59b knockout mice present a strong phenotype characterized by hemolytic anemia with increased reticulocytes, anisopoikilocytosis, echinocytosis, schistocytosis, free hemoglobin in plasma, hemoglobinuria with hemosiderinuria and platelet activation. Remarkably, mCd59b(-/-) males express a progressive loss of fertility associated with immobile dysmorphic and fewer sperm cells after 5 months of age. This work indicates that mCd59b is a key complement regulator in mice and that CD59 is critical in protecting self cells; it also provides a novel model to study complement regulation in human diseases.