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

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

Authors

Stewart Fleming

Nicholas D. Hastie

Charles E. Patek

Colin G. Miles

Christopher O. Bellamy

Lee Spraggon

John Mullins

Martin L. Hooper



Abstract

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

Citation

Hastie, N. D., Fleming, S., Patek, C. E., Miles, C. G., Bellamy, C. O., Ladomery, M., …Hooper, M. L. (2003). Murine Denys-Drash syndrome: Evidence of podocyte de-differentiation and systemic mediation of glomerulosclerosis. Human Molecular Genetics, 12(18), 2379-2394. https://doi.org/10.1093/hmg/ddg240

Journal Article Type Review
Publication Date Sep 15, 2003
Journal Human Molecular Genetics
Print ISSN 0964-6906
Publisher Oxford University Press (OUP)
Peer Reviewed Peer Reviewed
Volume 12
Issue 18
Pages 2379-2394
DOI https://doi.org/10.1093/hmg/ddg240
Public URL https://uwe-repository.worktribe.com/output/1074282
Publisher URL http://dx.doi.org/10.1093/hmg/ddg240