Modeling Human Diabetic Kidney Disease by Combining Hyperglycemia and Hypertension in a Transgenic Rodent Model

Methods Mol Biol. 2020:2067:41-52. doi: 10.1007/978-1-4939-9841-8_4.

Abstract

Traditional animal models mimic only the earliest stages of human diabetic nephropathy (DN), which limits their utility to dissect the pathogenesis of progressive disease or test novel therapeutics. In this chapter we describe in detail the experimental procedures required to conduct the Cyp1a1mRen2 rodent model, in which hyperglycemia and renin-dependent hypertension synergize to promote moderate proteinuria, renal fibrosis, and induction of many of the transcriptomic changes observed in the kidney of patients with progressive DN.

Keywords: Animal model; Diabetes; Hypertension; Nephropathy; Renin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytochrome P-450 CYP1A1 / genetics
  • Cytochrome P-450 Enzyme Inducers / pharmacology
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / complications*
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / pathology*
  • Disease Progression
  • Fibrosis
  • Humans
  • Hyperglycemia / chemically induced
  • Hyperglycemia / complications*
  • Hyperglycemia / genetics
  • Hypertension / complications*
  • Hypertension / genetics
  • Hypertension / metabolism
  • Indoles / pharmacology
  • Kidney / metabolism
  • Kidney / pathology*
  • Promoter Regions, Genetic / drug effects
  • Promoter Regions, Genetic / genetics
  • Rats
  • Rats, Transgenic
  • Renin / genetics
  • Renin / metabolism
  • Streptozocin / toxicity
  • Transcriptional Activation / drug effects

Substances

  • Cytochrome P-450 Enzyme Inducers
  • Indoles
  • Ren2 protein, mouse
  • Streptozocin
  • indole-3-carbinol
  • Cytochrome P-450 CYP1A1
  • Renin