A novel mouse model of podocyte depletion.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Wang, L; Tang, Y; Howell, DN; Ruiz, P; Spurney, RF

Published Date

  • 2012

Published In

Volume / Issue

  • 121 / 1-2

Start / End Page

  • e10 - e22

PubMed ID

  • 23095233

Pubmed Central ID

  • 23095233

Electronic International Standard Serial Number (EISSN)

  • 1660-2129

Digital Object Identifier (DOI)

  • 10.1159/000342369

Language

  • eng

Conference Location

  • Switzerland