An Update on the Use of Animal Models in Diabetic Nephropathy Research.

Boris Betz,Bryan R Conway

doi:10.1007/s11892-015-0706-2

Abstract

In the current review, we discuss limitations and recent advances in animal models of diabetic nephropathy (DN). As in human disease, genetic factors may determine disease severity with the murine FVB and DBA/2J strains being more susceptible to DN than C57BL/6J mice. On the black and tan, brachyuric (BTBR) background, leptin deficient (ob/ob) mice develop many of the pathological features of human DN. Hypertension synergises with hyperglycemia to promote nephropathy in rodents. Moderately hypertensive endothelial nitric oxide synthase (eNOS−/−) deficient diabetic mice develop hyaline arteriosclerosis and nodular glomerulosclerosis and induction of renin-dependent hypertension in diabetic Cyp1a1mRen2 rats mimics moderately severe human DN. In addition, diabetic eNOS−/− mice and Cyp1a1mRen2 rats recapitulate many of the molecular pathways activated in the human diabetic kidney. However, no model exhibits all the features of human DN; therefore, researchers should consider biochemical, pathological, and transcriptomic data in selecting the most appropriate model to study their molecules and pathways of interest.

Highlights

There are tentative signs that the incidence of endstage kidney disease due to diabetes is stabilizing, diabetic nephropathy (DN) remains the most common cause of endstage renal disease in the western world [1]
Improvements in the management of hyperglycemia and hypertension have reduced the proportion of patients with diabetes reaching endstage kidney disease [2]; additional therapies are required to target those with progressive renal disease
Animal models have been of limited utility in understanding the pathogenesis of DN, in part because no model exhibits all of the key features of human disease

Summary

Introduction

There are tentative signs that the incidence of endstage kidney disease due to diabetes is stabilizing, diabetic nephropathy (DN) remains the most common cause of endstage renal disease in the western world [1]. Improvements in the management of hyperglycemia and hypertension have reduced the proportion of patients with diabetes reaching endstage kidney disease [2]; additional therapies are required to target those with progressive renal disease. Rodent models have been useful in dissecting the pathogenesis of disease and for testing novel therapies. By introducing genetic modifications, specific cell types can be fluorescently tagged to track the fate of the cells over time or to facilitate isolation of cells from whole organs, and this may enhance our knowledge of disease pathogenesis. Targeted knockout or overexpression of genes can incisively determine the role of specific molecules in disease and whether such agents represent novel therapeutic

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Conclusion

Findings

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