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Nephrol Dial Transplant (2002) 17: 34-36
© 2002 European Renal Association-European Dialysis and Transplant Association


Glomerular Development and Pathology

Contribution of genetically engineered animals to the analyses of complement in the pathogenesis of nephritis

Norio Hanafusa, Hajime Sogabe, Koei Yamada, Takehiko Wada, Toshiro Fujita and Masaomi Nangaku

Division of Nephrology and Endocrinology, University of Tokyo, School of Medicine, Tokyo, Japan

Abstract

The complement system is indispensable for host defence. Unregulated activation, however, is related to various diseases. In order to elucidate the significance of complement, methodology that disrupts the complement system is essential. Advances in molecular genetics made direct modulations of the genes of complement components and their regulatory proteins feasible. One method is disruption of genes that encode complement components. Several studies have been conducted with these mice in models such as nephrotoxic serum (NTS) nephritis, ischaemia reperfusion and immune complex-mediated glomerulonephritis. These studies all showed that depletion of complement components ameliorated the severity of the diseases. Complement regulatory protein serves a regulatory role in the complement system. Genetically engineered animals that overexpress these proteins have been employed to elucidate their biological roles. Mice overexpressing soluble complement regulatory proteins were protected from the lesion of both NTS and the glomerular endothelial injury model. In contrast, knockout mice that lack expression of decay-accelerating factor (DAF), a complement regulatory protein, developed severe glomerular lesions when subnephritogenic doses of NTS were administered. These genetically engineered animals shed light on the mechanism of initiation and progression of kidney disease.

Keywords: complement; Crry; DAF; genetically engineered animal; nephritis; sCR1

Notes

Correspondence and offprint requests to: Masaomi Nangaku, MD, PhD, Division of Nephrology and Endocrinology, University of Tokyo, School of Medicine, 7–3–1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.


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M. Nangaku
Complement Regulatory Proteins: Are They Important in Disease?
J. Am. Soc. Nephrol., September 1, 2003; 14(9): 2411 - 2413.
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