Advertisement

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

  • Carolynn Cairns
  • Bryan ConwayEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 2067)

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.

Key words

Animal model Diabetes Hypertension Nephropathy Renin 

Notes

Acknowledgments

Dr. Conway was supported by a MRC Clinician Scientist Award, a Scottish Senior Clinical Fellowship, a British Heart Foundation Transition Fellowship Award, and grants from Kidney Research UK and the Edinburgh and Lothians Health Foundation Renal Fund.

References

  1. 1.
    Brosius FC 3rd, Alpers CE, Bottinger EP et al (2009) Mouse models of diabetic nephropathy. J Am Soc Nephrol 20:2503–2512CrossRefGoogle Scholar
  2. 2.
    Betz B, Conway BR (2016) An update on the use of animal models in diabetic nephropathy research. Curr Diab Rep 16:18CrossRefGoogle Scholar
  3. 3.
    Mogensen CE (1998) Combined high blood pressure and glucose in type 2 diabetes: double jeopardy. British trial shows clear effects of treatment, especially blood pressure reduction. BMJ 317:693–694CrossRefGoogle Scholar
  4. 4.
    Berkman J, Rifkin H (1973) Unilateral nodular diabetic glomerulosclerosis (Kimmelstiel-Wilson): report of a case. Metabolism 22:715–722CrossRefGoogle Scholar
  5. 5.
    Beroniade VC, Lefebvre R, Falardeau P (1987) Unilateral nodular diabetic glomerulosclerosis: recurrence of an experiment of nature. Am J Nephrol 7:55–59CrossRefGoogle Scholar
  6. 6.
    Kantachuvesiri S, Fleming S, Peters J et al (2001) Controlled hypertension, a transgenic toggle switch reveals differential mechanisms underlying vascular disease. J Biol Chem 276:36727–36733CrossRefGoogle Scholar
  7. 7.
    Conway BR, Rennie J, Bailey MA et al (2012) Hyperglycemia and renin-dependent hypertension synergize to model diabetic nephropathy. J Am Soc Nephrol 23:405–411CrossRefGoogle Scholar
  8. 8.
    Conway BR, Betz B, Sheldrake TA et al (2014) Tight blood glycaemic and blood pressure control in experimental diabetic nephropathy reduces extracellular matrix production without regression of fibrosis. Nephrology 19:802–813CrossRefGoogle Scholar
  9. 9.
    Liu X, Bellamy CO, Bailey MA et al (2009) Angiotensin-converting enzyme is a modifier of hypertensive end organ damage. J Biol Chem 284:15564–15572CrossRefGoogle Scholar
  10. 10.
    Kantachuvesiri S, Haley CS, Fleming S et al (1999) Genetic mapping of modifier loci affecting malignant hypertension in TGRmRen2 rats. Kidney Int 56:414–420CrossRefGoogle Scholar
  11. 11.
    Kelly DJ, Wilkinson-Berka JL, Allen TJ et al (1998) A new model of diabetic nephropathy with progressive renal impairment in the transgenic (mRen-2)27 rat (TGR). Kidney Int 54:343–352CrossRefGoogle Scholar
  12. 12.
    Hartner A, Cordasic N, Klanke B et al (2007) Renal injury in streptozotocin-diabetic Ren2-transgenic rats is mainly dependent on hypertension, not on diabetes. Am J Physiol Ren Physiol 292:F820–F827CrossRefGoogle Scholar
  13. 13.
    Keppler A, Gretz N, Schmidt R et al (2007) Plasma creatinine determination in mice and rats: an enzymatic method compares favorably with a high-performance liquid chromatography assay. Kidney Int 71:74–78CrossRefGoogle Scholar
  14. 14.
    Qi Z, Whitt I, Mehta A et al (2004) Serial determination of glomerular filtration rate in conscious mice using FITC-inulin clearance. Am J Physiol Ren Physiol 286:F590–F596CrossRefGoogle Scholar
  15. 15.
    Herrera Perez Z, Weinfurter S, Gretz N (2016) Transcutaneous assessment of renal function in conscious rodents. J Vis Exp 109:e53767Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Centre for Cardiovascular ScienceUniversity of EdinburghEdinburghUK

Personalised recommendations