Increased renal hypertrophy in diabetic mice genetically modified at the haptoglobin locus

Abstract

These results support a direct linkage between diabetic vascular disease and the Hp genotype. These Hp-modified mice may serve as a platform on which to test a variety of pharmacological agents in order to decrease diabetic vascular disease.

Retinal capillary basement membrane thickness in diabetic mice genetically modified at the haptoglobin locus

“…We have therefore sought to recapitulate the association of the Hp genotype and diabetic vascular disease in mice genetically modified at the Hp locus, where the only difference between the groups of mice is the Hp genotype. In the kidneys of these mice we have recently reported Hp genotype and DM‐dependent differences in renal hypertrophy, an early marker of diabetic renal disease 8. Thickening of microvascular basement membranes has been widely observed in diabetic humans and animals and is an early morphological characteristic of diabetic retinal disease 9.…”

The Genetics of Vascular Complications in Diabetes Mellitus

“…In the setting of DM, it has been shown by several groups that the Hp 2-2 polymorphism confers a 2-5 fold increased risk for CVD compared to the Hp 1-1 and Hp 2-1 genotype[188-192]. This was also seen in in vivo studies, where Hp 2-2 DM mice were more prone to develop retinopathy[193], nephropathy[194] and atherosclerosis[195, 196]. Interestingly in the absence of DM, the Hp 1-1 genotype may be associated with increased CVD[197, 198].…”

Haptoglobin genotype and its role in determining heme-iron mediated vascular disease

“…Specifically, diabetic Hp 2-2 transgenic mice showed a significant increase in renal and glomerular hypertrophy compared to diabetic Hp 1-1 mice [17]. No difference was found between Hp 2-2 and Hp 1-1 mice in the absence of diabetes.…”