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Characterization of zebrafish models of diabetic nephropathy Dan Konzman1, Fabien Delaspre2, Michael Parsons2, Raman Sood3, William A Gahl1,4, May Christine V. Malicdan1,4

Thursday, September 17, 2015 — Poster Session III

3:30 p.m. – 5:00 p.m.
FAES Terrace
NHGRI
CELLBIO-10

Authors

  • DW Konzman
  • F Delaspre
  • MJ Parsons
  • R Sood
  • WA Gahl
  • MC Malicdan

Abstract

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, and the increasing prevalence of diabetes is resulting in ever more cases of the disorder. New animal models are needed to help research progress novel therapies. Here, the efficacy of zebrafish as an emerging model of DN is explored. Research of neither diabetic nephropathy nor diabetes in general have made much use of the zebrafish model system. This organism holds potential for DN research due to its shorter development, making studies of this chronic disease more manageable and facilitating large group sizes. In this study we evaluated two modes of pancreatic ablation with the aim of reducing insulin secretion, thereby inducing diabetes. The first model is generated by injection of streptozotocin, a compound toxic solely to the pancreatic ß-cells, and this methodology’s ability to replicate diabetic and renal symptoms was assessed. One- and three-dose protocols were tested, and both methods showed histologic changes in the glomeruli. The second model, also tested for diabetic and kidney symptoms, was a transgenic model of pancreatic regeneration. This model fish uses a nitroreductase gene inserted with the Ins promoter, allowing ß-cells to be ablated in adulthood through metronidazole injection. Our results demonstrate that elevated glucose levels can be maintained through periodic injections and lead to altered renal histology. These models will prove powerful tools in the study of diabetic nephropathy. The results presented here provide a framework which future drug studies will be able to use to assess the efficacy of novel treatments.

Category: Cell Biology