NDT Advance Access originally published online on September 22, 2004
Nephrology Dialysis Transplantation 2004 19(11):2721-2728; doi:10.1093/ndt/gfh419
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Nephrol Dial Transplant Vol. 19 No. 11 © ERA-EDTA 2004; all rights reserved
Original Article
Mouse model of membranous nephropathy induced by cationic bovine serum albumin: antigen dose–response relations and strain differences
1 Graduate Institutes of Medical Sciences, 2 School of Pharmacy, National Defense Medical Center, 3 Division of Nephrology, Department of Internal Medicine, 4 Department of Pathology, Tri-Service General Hospital and5 National Health Research Institutes, Taipei, Taiwan
Correspondence and offprint requests to: Yuh-Feng Lin, MD, Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital 325, Sec. 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan, Republic of China. Email: linyf{at}ndmctsgh.edu.tw
Background. Few well-characterized animal models have been developed to study the pathogenesis of membranous nephropathy (MN). We have developed a mouse model of MN induced by cationic bovine serum albumin (cBSA), and examined the role of genetic background on disease induction by assessing different mouse strains.
Methods. cBSA in an optimum dose was given intravenously to 8-week-old female ICR, BALB/c and C57BL/6 mice for 4 weeks. The disease state was verified by renal histopathology as well as by serum and urine metabolic profiles. Serum concentrations of anti-cBSA immunoglobulins (Igs) and circulating immune complex (CIC) were assayed to study the mechanisms of initiation and progression. T-helper (Th) cell subsets in peripheral blood were examined using flow cytometry, and the Th1/Th2 subset distribution was determined by comparing the serum concentrations of IgG1 and IgG2a, using quantitative heterologous interpolation enzyme-linked immunosorbent assays.
Results. Only ICR and BALB/c mice developed the typical clinical and pathological patterns of MN in response to an optimum dose of cBSA. Disease induction was dose related and strain specific. The serum concentrations of anti-cBSA were significantly higher in the strains that developed MN, but there were no differences in CIC concentrations. This suggests that in situ immune-complex glomerulonephritis may be involved in the development of MN. The Th2 type immune response may predominate in the ICR and BALB/c mice models, as the serum concentration of IgG1 was higher than that of IgG2a; moreover Th2 type strain specificity was necessary for the development of MN.
Conclusions. This improved mouse model of MN induced by cBSA more closely duplicates human MN than the other available models. Disease generation is antigen dose related and strain specific.
Keywords: cationic bovine serum albumin; circulating immune complex; membranous nephropathy; strain difference; T-helper lymphocytes
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