A novel mouse model of podocyte depletion

L. Wang, Y. Tang, D. N. Howell, P. Ruiz, R. F. Spurney

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Aim: The goal of this study was to examine the capacity for glomerular repair after a podocyte-depleting injury. Methods: We created transgenic (TG) mice expressing the yeast enzyme cytosine deaminase specifically in glomerular podocytes. In these TG animals, the prodrug 5-flucytosine (5-FC) is converted to 5-fluorouracil and promotes cell death. Results: Treatment with increasing dosages of 5-FC caused graded increases in proteinuria 1-2 weeks after treatment, which returned to control levels by the 10-week time point. Light microscopic examination revealed minimal pathology at the 2-week time point, but electron microscopy revealed found foot process effacement as well as focal areas of glomerular basement membrane duplication, and immunohistochemical studies detected podocyte apoptosis and a decrease in the number of Wilms' tumor protein 1 (WT1)-positive cells. By the 10-week time point, however, the number of WT1-positive cells was similar to controls and a few mice had developed focal areas of glomerulosclerosis. Consistent with the effects of 5-FC on podocyte number, expression of the podocyte mRNAs for nephrin, podocin, synaptopodin and podocalyxin were altered in a similar temporal fashion. Conclusion: The glomerulus has a significant capacity for repair after a podocyte-depleting injury.

Original languageEnglish (US)
Pages (from-to)e10-e22
JournalNephron - Experimental Nephrology
Volume121
Issue number1-2
DOIs
StatePublished - Dec 2012

Keywords

  • Glomerular disease
  • Mouse model
  • Podocyte

ASJC Scopus subject areas

  • Nephrology
  • Physiology
  • Genetics

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