Mouse model of membranous nephropathy induced by cationic bovine serum albumin: antigen dose-response relations and strain differences
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Published on: May 6, 2018
Jin-Shuen Chen1, Ann Chen, Li-Chien Chang
1Graduate Institutes of Medical Sciences, Taipei, Taiwan.
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.
Insights
A new mouse model using cationic bovine serum albumin (cBSA) effectively replicates human membranous nephropathy (MN). Disease development in this model is dependent on both the antigen dose and the specific mouse strain, highlighting genetic factors in MN pathogenesis.
Area of Science:
- Nephrology
- Immunology
- Animal models
Background:
- Membranous nephropathy (MN) pathogenesis lacks well-characterized animal models.
- Development of a novel mouse model for MN using cationic bovine serum albumin (cBSA).
Purpose of the Study:
- To establish and validate a cBSA-induced mouse model for studying MN.
- To investigate the influence of genetic background on MN induction.
Main Methods:
- Administration of cBSA to ICR, BALB/c, and C57BL/6 mice.
- Assessment of renal histopathology, metabolic profiles, anti-cBSA immunoglobulins (Igs), and circulating immune complexes (CIC).
- Flow cytometry analysis of T-helper (Th) cell subsets and IgG subclass quantification.
Main Results:
- ICR and BALB/c mice developed MN, while C57BL/6 mice did not, indicating strain specificity.
- Disease induction was dose-dependent and strain-specific.
- Elevated anti-cBSA Ig levels in MN-affected strains suggest in situ immune complex formation; a predominant Th2 immune response was observed.
Conclusions:
- The cBSA-induced mouse model closely mimics human MN.
- MN development is antigen dose-related and strain-specific, emphasizing the role of genetic background.
