Strain specific responses of inbred rats on the severity of experimental autoimmune glomerulonephritis

Experimental autoimmune glomerulonephritis with pulmonary hemorrhage was induced in rats of 4 inbred strains, F344/DuCrj, LEW/Crj, WKY/NCrj and SHR/NCrj, by the injection of a nephritogenic antigen from bovine glomerular basement membrane. The severity and clinical course of glomerulonephritis within the strains were very similar, but those between the strains were different. Among them, F344 rats demonstrated mild glomerulonephritis with petechial pulmonary hemorrhage. LEW rats showed more severe symptoms from pulmonary hemorrhage than F344 rats and had heavy, long-lasting proteinuria that caused nephrotic syndrome. WKY rats showed very severe glomerulonephritis with pulmonary hemorrhage, and had azotemia by 4 weeks after the injection. SHR rats had both severe glomerulonephritis and severe pulmonary hemorrhage. Investigation of the dose-effect relationship of the nephritogenic antigen in F344 and WKY rats revealed that the minimum dose required to induce nephritis in F344 and WKY rats was 10 micrograms and 3 micrograms respectively, and that the injection of more than a certain amount (i.e., 30 micrograms in F344, 10 micrograms in WKY) of the antigenic material induced almost the same severity of disease. These results indicate that genetic differences in experimental animals influence the severity of renal damage, suggesting that the use of inbred strains is necessary for adequate study of experimental glomerulonephritis.