Mouse model of membranous nephropathy induced by cationic bovine serum albumin: Antigen dose-response relations and strain differences

Jin Shuen Chen, Ann Chen, Li Chien Chang, W. S W Chang, Herng Sheng Lee, Shih H. Lin, Yuh Feng Lin

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2721-2728
Number of pages8
JournalNephrology Dialysis Transplantation
Volume19
Issue number11
DOIs
Publication statusPublished - Nov 2004
Externally publishedYes

Keywords

  • Cationic bovine serum albumin
  • Circulating immune complex
  • Membranous nephropathy
  • Strain difference
  • T-helper lymphocytes

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

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