Spontaneous glomerular IgA deposition in ddY mice: An animal model of IgA nephritis

Abstract

It was found that ddY mice derived from non-inbred dd-stock mice brought from Germany before 1920 and then raised in Japan developed spontaneously IgA dominant deposition in the glomerular mesangium. In this report we give a detailed natural history of the renal pathology of those mice. The animals were fed rodent laboratory chow and sacrificed in groups of 9 to 10 at 6, 10, 16, 24, 28, 40, and 59 weeks of age. The bladder urine was analyzed, serum immunoglobulins were measured, and the kidney specimens were evaluated with light, fluorescent, and electron microscopy. Proteinuria was (+) to (++) after 28 weeks and (++) to (+++) at 59 weeks with negative hematuria. Mesangial cell proliferation began to appear at 16 weeks, then progressed to a definite proliferative glomerulonephritis. At 59 weeks an additional increase of the mesangial matrix occurred. By immunofluorescence, there were IgG of (++) , IgM (+) to (++), IgA (+) and C3 (+) in the glomeruli until 28 weeks. However, IgA started to be dominant at 40 weeks and the glomerular pattern was IgA (++) to (+++), IgG (+) to (++), IgM (±) to (+) and C3 (+) to (++) at 59 weeks. Polyclonal IgA and IgG(2α) among immunoglobulins steeply rose at 40 weeks, and at 59 weeks IgA increased by 850%, IgG(2α) by 280%, IgG1 by 170%, IgG(2b) by 90%, and IgM by 60%, as compared with their level at 6 weeks. There was no anti-nuclear antibody. Thus, ddY mice, at least after the age of 40 weeks, can be used as a new animal model for spontaneous IgA nephritis. The probable origin of IgA is also discussed.