Complications of IgA Nephropathy in a Non-Insulin-Dependent Diabetes Model, the Akita Mouse

Complications of IgA Nephropathy in a Non-Insulin-Dependent
Diabetes Model, the Akita Mouse

TOSHIYUKI HASEYAMA,^1,2 TOSHIKI FUJITA,¹ FUJIKO HIRASAWA,¹ MIKAKO TSUKADA,^1,3
HIDEKI WAKUI,² ATSUSHI KOMATSUDA,² HIROSHI OHTANI,² AKIRA B. MIURA,²
HIROKAZU IMAI² and AKIO KOIZUMI^1,4

¹Department of Hygiene, ²The Third Department of Internal Medicine, Akita University School of Medicine, Akita 010-8543,
³Department of Life and Nutrition, Seirei Women's College Akita 010-8543, and ⁴Department of Health and Environmental Sciences, Kyoto University School of Public Health, Kyoto 606-8501

The Akita mouse, which has a mutation (Cys96Tyr) in the insulin 2 gene (Ins2^Akita), is a model for diabetes. The male Akita mouse has diabetes, while females develop mild diabetes. This study aimed to investigate renal complications in the Akita mouse model, which has been maintained in a heterozygous state Ins2^Akita (+/–) with a C57BL/6 background (B6). Renal function (BUN, creatinine), serum IgA concentrations and histological changes in the kidneys were evaluated in diabetic and control mice in a B6 background. Five each of male and female mice per group (diabetes vs. control) were killed at 10, 20, 30 and 40 weeks of age. The influence of major histocompatibility antigens (MHC) on renal complications was tested using male diabetic mice in a C3H/He (C3H) background. When compared with controls, diabetic males, but not females, developed impaired renal function with elevation of serum IgA after 30 weeks of age. Diabetic glomerulosclerosis advanced with age in both sexes. Diffuse granular mesangial deposits of IgA were detected by immunofluorescence microscopy in diabetic males after 20 weeks. We tested whether the IgA-associated lesions were influenced by MHC using diabetic males in a C3H background. Similar degrees of diabetic glomerulosclerosis and glomerular IgA deposition were found in mice with C3H and B6 backgrounds. Akita mouse is a unique mouse model showing both mesangial sclerosis and IgA nephropathy.

Keywords —— C57BL/6 Akita mouse; diabetic glomerulosclerosis; glomerular IgA deposition; MHC

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Tohoku J. Exp. Med., 2002, 198, 233-244

Address for reprints: Prof. Akio Koizumi, M.D., Ph.D., Department of Health and Environmental Sciences, Kyoto University School of Public Health, Kyoto 606-8501, Japan.

e-mail: koizumi@pbh.med.kyoto-u.ac.jp