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 (plus) to (2 plus) after 28 weeks and (2 plus) to (3 plus) 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 (2 plus), IgM (plus) to (2 plus), IgA (plus) and C3 (plus) in the glomeruli until 28 weeks. However, IgA started to be dominant at 40 weeks and the glomerular pattern was IgA (2 plus) to (3 plus), IgG (plus) to (2 plus), IgM (+/-) to (plus) and C3 (plus) to (2 plus) at 59 weeks. Polyclonal IgA and IgG2a among immunoglobulins steeply rose at 40 weeks, and at 59 weeks IgA increased by 850%, IgG2a by 280%, IgG1 by 170%, IgG2b 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.

Age-dependent decrease of polymeric Ig receptor expression and IgA elevation in ddY mice: a possible cause of IgA nephropathy

“…The other was the ddY Norm mice population with the IgA level within the mean 72 s.d.s of BALB/c mice throughout the whole course of the experiment. This result was consistent with the genetic segregation analysis observed in the closed-colony ddY population carried out by Imai et al 8 Next, we studied the age-dependent changes of urinary IgA concentration in ddY mice. Although we could also observe the elevation of IgA in urine among ddY High mice to some extent, the magnitude of age-dependent IgA increase in urine was very low.…”

“…8 We found that we could classify ddY mice into at least two subgroups. One was a HIGA group that exhibited some symptoms of IgAN through aging (ddY High ), and the other was a normal serum IgA group without IgAN (ddY Norm ).…”

Development of immune-complex glomerulonephritis in athymic mice: T cells are not required for the genesis of glomerular injury

“…23 Indeed, among the murine models of IgAN, those with hematuria and glomerular dysfunction are typically the ones with mesangial complement deposition; [23][24][25][26] conversely, those without complement generally have normal glomerular function. [27][28][29] However, in the system described herein, a pathogenic role for the complement system is improbable, since hematuria occurred even in mice with little or no glomerular C3 deposits.…”

Family-Based Association Study Showing that Immunoglobulin A Nephropathy Is Associated with the Polymorphisms 2093C and 2180T in the 3′ Untranslated Region of the Megsin Gene

“…Epidemiologic studies suggest a significant difference in the incidence/prevalence among different ethnic groups and support significant familial aggregation (6). Data from mouse studies, including the outbred strain ddY (8) and knockout and transgenic approaches (9 -11), have shown that specific genetic alterations in a model organism give rise to a phenotype that shares features with the human disease.…”