title: A novel mouse model of podocyte depletion.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  The glomerulus has a significant capacity for repair after a podocyte-depleting injury.
authors.affiliation: Division of Nephrology, Department of Medicine, Duke University and Durham VA Medical Centers, Durham, NC 27710, USA. spurn002 @ mc.duke.edu
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Tang
authors.forename: D N
authors.initials: DN
authors.lastname: Howell
authors.forename: P
authors.initials: P
authors.lastname: Ruiz
authors.forename: R F
authors.initials: RF
authors.lastname: Spurney
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D000818:Animals; D000963:Antimetabolites; D043525:Cytosine Deaminase / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005437:Flucytosine; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology*; D011507:Proteinuria / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D020127:Recovery of Function
chemical_list: D000963:Antimetabolites; D005437:Flucytosine; D043525:Cytosine Deaminase