Analysis of C4 and the C4 binding protein in the MRL/lpr mouse |
| |
Authors: | Scott E Wenderfer Kipruto Soimo Rick A Wetsel Michael C Braun |
| |
Institution: | (1) Center for Immunology and Autoimmune Diseases, Brown Foundation Institute of Molecular Medicine, 1825 Pressler Street, Houston, 77030, TX, USA;(2) Pediatric Nephrology, University of Texas, 6431 Fannin Street, Houston, 77030, TX, USA |
| |
Abstract: | 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. |
| |
Keywords: | |
本文献已被 PubMed SpringerLink 等数据库收录! |
|