| First Author | Wang L | Year | 2012 |
| Journal | Nephron Exp Nephrol | Volume | 121 |
| Issue | 1-2 | Pages | e10-22 |
| PubMed ID | 23095233 | Mgi Jnum | J:221847 |
| Mgi Id | MGI:5641625 | Doi | 10.1159/000342369 |
| Citation | Wang L, et al. (2012) A novel mouse model of podocyte depletion. Nephron Exp Nephrol 121(1-2):e10-22 |
| abstractText | 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. |
