Experimental model of membranous nephropathy in mice: sequence of histological and biochemical events.
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.
Wu
Chia-Chao
CC
Graduate Institute of Medical Science, Tri-Service General Hospital, Taipei, Taiwan.
Chen
Jin-Shuen
JS
Lin
Shih-Hua
SH
Chen
Ann
A
Sytwu
Huey-Kang
HK
Lin
Yuh-Feng
YF
D000818:Animals; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000097:blood / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D006651:Histocytochemistry; D006937:Hypercholesterolemia / Q000097:blood; D034141:Hypoalbuminemia / Q000097:blood; D007132:Immunoglobulin Isotypes / Q000097:blood; D007136:Immunoglobulins / Q000097:blood*; D007668:Kidney / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D011507:Proteinuria / Q000097:blood; D011897:Random Allocation; D013047:Specific Pathogen-Free Organisms; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D007132:Immunoglobulin Isotypes; D007136:Immunoglobulins; D003404:Creatinine