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Publication

Characterization of Diabetic Nephropathy in a Transgenic Model of Nonobese Diabetes

Authors Yukiko Kanetsuna, Keita Hirano, Michio Nagata, Maureen A Gannon, Raymond C. Harris, Matthew D. Breyer, and Takamune Takahashi Submitted By Matthew Breyer on 9/6/2005 Status Published Journal American journal of physiology. Renal physiology Year 2006 Date Published 12/1/2006 Volume : Pages 291(6) : F1315 - F1322 PubMed Reference 16705146 Abstract Genetic mouse models provide a unique opportunity to investigate gene function in the natural course of the disease. Although diabetic nephropathy (DN) in models of type II diabetes has been well characterized, diabetic renal disease in nonobese diabetic mice is still incompletely understood. Here, we characterized renal changes in the pdx1PB-HNF6 transgenic mouse that exhibits β-cell dysfunction and nonobese diabetes. Male transgenics developed hyperglycemia by the age of 7 weeks and survived over a year without insulin treatment. Diabetes ensued earlier and progressed more severely in the HNF6 males than the females. The HNF6 males exhibited albuminuria as early as 10 weeks of age and the urinary albumin excretion increased with age, exceeding 150 µg/24 h at 11 months of age. Diabetic males developed renal hypertrophy after 7 weeks of age, whereas glomerular hyperfiltration was not observed in the mice. Hypertension and hyperlipidemia were not observed in the diabetic mice. Histological analysis of the HNF6 kidneys displayed diabetic glomerular changes, including glomerular enlargement, diffuse mesangial proliferation and matrix expansion, thickened glomerular basement membrane and arteriolar hyalinosis. Mesangial matrix accumulation increased with age, resulting in nodular lesions by 44 weeks of age. Immunohistochemistry showed accumulation of type IV collagen and TGFβ1 in the mesangial area. No significant immune complex deposition was observed in the HNF6 glomeruli. Thus, the HNF6 mouse exhibits diabetic renal changes that parallel the early phase of human DN. The model should facilitate studies of genetic and environmental factors that may affect DN in nonobese diabetes.

Complications
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Genes
Symbol Description Onecut1 one cut domain, family member 1 Tgfb1 transforming growth factor, beta 1 Alb albumin