Murine Denys-Drash syndrome: evidence of podocyte de-differentiation and systemic mediation of glomerulosclerosis

Charles E Patek, Stewart Fleming, Colin G Miles, Christopher O Bellamy, Michael Ladomery, Lee Spraggon, John Mullins, Nicholas D Hastie, Martin L Hooper

Research output: Contribution to journalArticlepeer-review


Denys-Drash syndrome (DDS) is caused by dominant mutations of the Wilms' tumour suppressor gene, WT1, and characterized by a nephropathy involving diffuse mesangial sclerosis, male pseudohermaphroditism and/or Wilms' tumourigenesis. Previously, we reported that heterozygosity for the Wt1tmT396 mutation induces DDS in heterozygous and chimeric (Wt1tmT396/++/+) mice. In the present study, the fate of Wt1 mutant cells in chimeric kidneys was assessed by in situ marker analysis, and immunocytochemistry was used to re-examine the claim that glomerulosclerosis (GS) is caused by loss of WT1 and persistent Pax-2 expression by podocytes. Wt1 mutant cells colonized glomeruli efficiently, including podocytes, but some sclerotic glomeruli contained no detectable Wt1 mutant cells. The development of GS was preceded by widespread loss of ZO-1 signal in podocytes (even in kidneys where
Original languageEnglish
Pages (from-to)2379-94
Number of pages16
JournalHuman Molecular Genetics
Issue number18
Publication statusPublished - 15 Sep 2003


  • Animals
  • Cell Differentiation
  • DNA
  • Denys-Drash Syndrome
  • Gene Expression
  • Genes, Dominant
  • Genes, Tumor Suppressor
  • Genetic Markers
  • Glomerulonephritis
  • Glucose-6-Phosphate Isomerase
  • Heterozygote
  • Immunohistochemistry
  • In Situ Hybridization
  • Kidney Glomerulus
  • Membrane Proteins
  • Mice
  • Mice, Knockout
  • Mutation
  • Phosphoproteins
  • Renin
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • WT1 Proteins
  • Zonula Occludens-1 Protein


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