Analysis of C4 and the C4 binding protein in the MRL/lpr mouse.
Analysis of C4 and the C4 binding protein in the MRL/lpr mouse.
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DOI：
10.1186/ar2320
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发表时间：
2007
影响因子：
4.9
通讯作者：
Braun, Michael C.
中科院分区：
文献类型：
--
作者：
Wenderfer, Scott E.;Soimo, Kipruto;Wetsel, Rick A.;Braun, Michael C.
系统性红斑狼疮是一种补体介导的自身免疫性疾病。虽然经典途径组分的遗传缺陷导致发生系统性红斑狼疮的风险增加，但终末器官损伤与补体激活和免疫复合物沉积相关。经典途径调节因子在系统性红斑狼疮中的作用尚不清楚。C4结合蛋白（C4 bp）是经典途径的主要负调节因子。为了研究C4 bp缺陷在已建立的狼疮肾炎小鼠模型中的作用，将编码C4 bp的基因中具有靶向缺失的小鼠回交到MRL/lpr遗传背景中。与对照MRL/lpr小鼠相比，C4 bp基因敲除MLR/lpr小鼠具有相似的死亡率和相似程度的淋巴细胞增殖。蛋白尿或肾脏炎症的程度没有差异。对患病小鼠肾脏中的补体蛋白和免疫球蛋白进行染色，结果显示没有显著的品系差异。此外，在自身抗体的产生或循环免疫复合物的水平方面没有差异。与C57 BL/6小鼠相比，MRL/lpr小鼠早在3周龄时就降低了C4水平。C4 bp的缺失不影响血清C4水平或改变经典途径溶血活性。鉴于MRL/lpr小鼠中的免疫复合物肾损伤不依赖于Fc受体以及经典途径的主要负调节因子，因此需要考虑免疫复合物介导的肾损伤的新机制。
Systemic lupus erythematosus is a complement-mediated autoimmune disease. While genetic deficiencies of classical pathway components lead to an increased risk of developing systemic lupus erythematosus, end organ damage is associated with complement activation and immune complex deposition. The role of classical pathway regulators in systemic lupus erythematosus is unknown. C4 binding protein (C4bp) is a major negative regulator of the classical pathway. In order to study the role of C4bp deficiency in an established murine model of lupus nephritis, mice with a targeted deletion in the gene encoding C4bp were backcrossed into the MRL/lpr genetic background. Compared with control MRL/lpr mice, C4bp knockout MLR/lpr mice had similar mortality and similar degrees of lymphoproliferation. There were no differences in the extent of proteinuria or renal inflammation. Staining for complement proteins and immunoglobulins in the kidneys of diseased mice revealed no significant strain differences. Moreover, there was no difference in autoantibody production or in levels of circulating immune complexes. In comparison with C57BL/6 mice, MRL/lpr mice had depressed C4 levels as early as 3 weeks of age. The absence of C4bp did not impact serum C4 levels or alter classical pathway hemolytic activity. Given that immune complex renal injury in the MRL/lpr mouse is independent of Fc receptors as well as the major negative regulator of the classical pathway, new mechanisms for immune-complex-mediated renal injury need to be considered.
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影响因子：
--
作者：
Matsumoto, K;Watanabe, N;Saito, T
通讯作者：
Saito, T
影响因子：
32.4
作者：
Brodeur, SR;Angelini, F;Geha, RS
通讯作者：
Geha, RS
DOI：
10.1073/pnas.76.12.6596
发表时间：
1979-01-01
影响因子：
11.1
作者：
GIGLI, I;FUJITA, T;NUSSENZWEIG, V
通讯作者：
NUSSENZWEIG, V
影响因子：
1
作者：
Hicks, John;Bullard, Daniel C.
通讯作者：
Bullard, Daniel C.
影响因子：
5
作者：
Kono, D H;Theofilopoulos, A N
通讯作者：
Theofilopoulos, A N