Ultrastructural and functional analyses of nephropathy in calmodulin-induced diabetic transgenic mice

The Anatomical Record
E C CarlsonPaul N Epstein

Abstract

Previous animal models of diabetic nephropathy have used diabetic animals for which the underlying defect was either uncertain or the diabetes was induced by potentially specific toxins. In this report, we describe the renal abnormalities in a transgenic mouse model that develops early-onset diabetes due to overexpression of calmodulin in pancreatic beta cells. Renal tissues were collected from normal and transgenic mice at 112, 182, and 300 days. These were prepared for light microscopic observation, stained with polyethylenimine (for anionic sites), or rendered acellular by detergent extraction prior to observation by transmission and scanning electron microscopy. Morphometric analysis of glomerular basement membrane thickness was carried out by the "orthogonal intercept" method. Twelve-hour urine samples of fed and fasting mice were collected for urine volume and glucose and protein analyses. Blood glucose, blood urea nitrogen, serum insulin, and creatinine were determined in 60-90-day-old and 255-day-old mice by established methods. Morphometric analyses revealed age-related and transgene-related increases in glomerular basement membrane thickness. A 22% increase in transgenic diabetics over controls was seen at 112 days of...Continue Reading

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Citations

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Jun 6, 2008·Journal of the American Society of Nephrology : JASN·Yukio YuzawaSeiichi Matsuo
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