An immune complex glomerulopathy associated with glomerular capillary thrombosis in the laboratory mouse. A highly reproducible accelerated model utilizing cationized antigen

Abstract

An accelerated, highly reproducible model of an immune complex glomerulopathy in the laboratory mouse was developed by using cationized bovine gamma-globulin (cat-BGG) as the nephritogenic agent. Preimmunized Balb/c mice given three 250-micrograms doses of cat-BGG consistently develop a nonproliferative glomerular lesion which becomes manifested clinically by the nephrotic syndrome and results in death within 14 days. Significant proteinuria is evident by day 4 (24 hours after the third dose of cat-BGG) at which time extensive deposits of cat-BGG, IgG, and C3 are localized along the glomerular capillary walls. At the ultrastructural level, subepithelial deposits and foot process effacement are evident. By day 6, subendothelial and mesangial deposits are also present, and by day 10, extensive glomerular capillary thrombosis and early crescent formation develop. The reproducibility and rapidity of the induction of disease, and the spectrum of pathological changes occurring in the glomeruli make this murine model of an immune complex glomerulopathy potentially useful for the study of the mechanisms underlying the induction and progression of glomerular injury and the evaluation of potential therapy.