Experimental model of membranous nephropathy in mice: Sequence of histological and biochemical events

Chia Chao Wu, Jin Shuen Chen, Shih Hua Lin, Ann Chen, Huey Kang Sytwu, Yuh Feng Lin

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

An experimental model of membranous nephropathy (MN) has not been established fully in mice. We characterized the time course of MN in a murine MN model induced by cationic bovine serum albumin (cBSA). Preimmunized mice received cBSA intravenously for six weeks to induce MN and were then sacrificed at different times. Metabolic profiles, renal histopathology, lymphocyte subsets, serum anti-cBSA immunoglobulins (Igs), antibody subclasses and circulating immune complexes (CIC) were evaluated to study the severity and mechanisms of disease initiation and progression. Clinical symptoms of overt proteinuria, hypoalbuminaemia and hypercholesterolaemia were observed from week 4, and typical histological findings of diffuse thickening of the glomerular basement membrane and subepithelial deposition were identified after week 6. Granular fluorescent staining for IgG and complement C3 were observed as early as week 4. Total splenocyte number increased, but the percentages of CD4+ and CD8+ cells did not change as the disease progressed. The predominant isotype of anti-cBSA Igs was IgG1, suggesting a T-helper 2 cell-prone immune response in the development of MN. The strong positive immunofluorescent staining of the immune complex concomitant with higher concentrations of Igs in serum but no significant change in CIC levels before week 4 suggest the involvement of in situ deposition of immune complex in the process of MN. This murine model resembles the clinical and pathological features of human MN and may provide a tool for investigating MN; this model may also have potential applications in gene-knockout or transgenic mouse technologies.

Original languageEnglish
Pages (from-to)350-359
Number of pages10
JournalLaboratory Animals
Volume42
Issue number3
DOIs
Publication statusPublished - Jul 2008
Externally publishedYes

Fingerprint

Membranous Glomerulonephritis
kidney diseases
Theoretical Models
antigen-antibody complex
mice
bovine serum albumin
Bovine Serum Albumin
Antigen-Antibody Complex
immunoglobulins
Immunoglobulins
Immunoglobulin G
Staining and Labeling
Hypoalbuminemia
Th2 Cells
Glomerular Basement Membrane
Gene Knockout Techniques
Complement C3
Metabolome
hypercholesterolemia
Lymphocyte Subsets

Keywords

  • Animal model
  • Membranous nephropathy
  • Mouse
  • Proteinuria

ASJC Scopus subject areas

  • Animal Science and Zoology
  • veterinary(all)

Cite this

Experimental model of membranous nephropathy in mice : Sequence of histological and biochemical events. / Wu, Chia Chao; Chen, Jin Shuen; Lin, Shih Hua; Chen, Ann; Sytwu, Huey Kang; Lin, Yuh Feng.

In: Laboratory Animals, Vol. 42, No. 3, 07.2008, p. 350-359.

Research output: Contribution to journalArticle

Wu, Chia Chao ; Chen, Jin Shuen ; Lin, Shih Hua ; Chen, Ann ; Sytwu, Huey Kang ; Lin, Yuh Feng. / Experimental model of membranous nephropathy in mice : Sequence of histological and biochemical events. In: Laboratory Animals. 2008 ; Vol. 42, No. 3. pp. 350-359.
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