CD59a is the primary regulator of membrane attack complex assembly in the mouse
CD59a is the primary regulator of membrane attack complex assembly in the mouse
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DOI：
10.4049/jimmunol.173.6.3684
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发表时间：
2004-09-15
影响因子：
4.4
通讯作者：
Morgan, BP
中科院分区：
文献类型：
--
作者：
Baalasubramanian, S;Harris, CL;Morgan, BP
基因缺失的小鼠为了解补体和补体调节蛋白在体内的作用提供了一个强有力的工具。特别是，缺乏膜调节剂补体受体1相关基因/蛋白y、衰变加速因子或CD59的小鼠已经证明了体内平衡的相关性，并且品系之间的回交在调节方面表现出了协同性。在小鼠中，编码衰变加速因子和CD59的基因已经复制，并在组织中显示出差异表达，这使得对人类的研究结果的解释和推断变得复杂。CD59的第一种形式CD59a分布广泛，在补体介导的疾病模型中，cd59a基因的缺失会导致轻度溶血表型，增加易感性。第二种形式CD59b的分布最初被描述为睾丸特有的，但后来被一些人描述为广泛分布。Cd59b基因缺失导致严重的溶血和血栓表型。为了将这些小鼠模型的数据应用于人类，了解这两种形式的CD59的相对分布和功能作用是至关重要的。我们开发了新的特异性试剂，并将其用于灵敏的定量分析，以全面表征CD59a和CD59b在野生型(Wt)和CD59a阴性小鼠中的mRNA和蛋白表达及其功能作用。Cd59b基因只在睾丸中检测到，在很低水平的骨髓中也检测到。CD59b蛋白存在于成熟精子和前体细胞以及微量的红细胞中。除CD59a缺失或被阻断外，红细胞CD59b不抑制补体溶解。这些数据证实了CD59a是小鼠补体膜攻击的主要调节因子。
Gene-deleted mice have provided a potent tool in efforts to understand the roles of complement and complement-regulating proteins in vivo. In particular, mice deficient in the membrane regulators complement receptor 1-related gene/protein y, decay-accelerating factor, or CD59 have demonstrated homeostatic relevance and backcrossing between the strains has revealed cooperativity in regulation. In mouse, genes encoding decay-accelerating factor and CD59 have been duplicated and show differential expression in tissues, complicating interpretation and extrapolation of findings to man. The first described form of CD59, CD59a, is broadly distributed and deletion of the cd59a gene causes a mild hemolytic phenotype with increased susceptibility in complement-mediated disease models. The distribution of the second form, CD59b, was originally described as testis specific, but later by some as widespread. Deletion of the cd59b gene caused a severe hemolytic and thrombotic phenotype. To apply data from these mouse models to man it is essential to know the relative distribution and functional roles of these two forms of CD59. We have generated new specific reagents and used them in sensitive quantitative analyses to comprehensively characterize expression of mRNA and protein and functional roles of CD59a and CD59b in wild-type (wt) and CD59a-negative mice. cd59b mRNA was detected only in testis and, at very low levels, in bone marrow. CD59b protein was present on mature spermatozoa and precursors and, in trace amounts, erythrocytes. Erythrocyte CD59b did not inhibit complement lysis except when CD59a was absent or blocked. These data confirm that CD59a is the primary regulator of complement membrane attack in mouse.