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A novel mouse model of podocyte depletion.

Publication ,  Journal Article
Wang, L; Tang, Y; Howell, DN; Ruiz, P; Spurney, RF
Published in: Nephron Exp Nephrol
2012

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.

Duke Scholars

Published In

Nephron Exp Nephrol

DOI

EISSN

1660-2129

Publication Date

2012

Volume

121

Issue

1-2

Start / End Page

e10 / e22

Location

Switzerland

Related Subject Headings

  • Urology & Nephrology
  • Recovery of Function
  • Proteinuria
  • Podocytes
  • Mice, Transgenic
  • Mice
  • Kidney
  • Humans
  • Flucytosine
  • Disease Models, Animal
 

Citation

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Wang, L., Tang, Y., Howell, D. N., Ruiz, P., & Spurney, R. F. (2012). A novel mouse model of podocyte depletion. Nephron Exp Nephrol, 121(1–2), e10–e22. https://doi.org/10.1159/000342369
Wang, L., Y. Tang, D. N. Howell, P. Ruiz, and R. F. Spurney. “A novel mouse model of podocyte depletion.Nephron Exp Nephrol 121, no. 1–2 (2012): e10–22. https://doi.org/10.1159/000342369.
Wang L, Tang Y, Howell DN, Ruiz P, Spurney RF. A novel mouse model of podocyte depletion. Nephron Exp Nephrol. 2012;121(1–2):e10–22.
Wang, L., et al. “A novel mouse model of podocyte depletion.Nephron Exp Nephrol, vol. 121, no. 1–2, 2012, pp. e10–22. Pubmed, doi:10.1159/000342369.
Wang L, Tang Y, Howell DN, Ruiz P, Spurney RF. A novel mouse model of podocyte depletion. Nephron Exp Nephrol. 2012;121(1–2):e10–e22.
Journal cover image

Published In

Nephron Exp Nephrol

DOI

EISSN

1660-2129

Publication Date

2012

Volume

121

Issue

1-2

Start / End Page

e10 / e22

Location

Switzerland

Related Subject Headings

  • Urology & Nephrology
  • Recovery of Function
  • Proteinuria
  • Podocytes
  • Mice, Transgenic
  • Mice
  • Kidney
  • Humans
  • Flucytosine
  • Disease Models, Animal