beta-Catenin mediates adriamycin-induced albuminuria and podocyte injury in adult mouse kidneys

Nephrol Dial Transplant. 2010 Aug;25(8):2437-46. doi: 10.1093/ndt/gfq076. Epub 2010 Mar 17.


Background: Glomerular slit diaphragm (SD) represents a modified adherens junction composed of molecules belonging to both immunoglobulin and cadherin superfamilies. Cadherins associate with the cytosolic scaffolding protein beta-catenin, but the precise role of beta-catenin in mature or injured podocytes is not known.

Methods: The conditional podocyte-specific beta-catenin-deficient mouse line was generated using the doxycycline-inducible Cre-loxP system. Expression of the beta-catenin-deficient gene was turned off at the age of 8 weeks by doxycycline treatment and the kidney phenotype was analysed. In addition, beta-catenin-deficient and control mice were treated with adriamycin (ADR) and analysed for albuminuria and morphological alterations.

Results: Deletion of beta-catenin in mature podocytes did not change the morphology of podocytes nor did it lead to albuminuria. However, lack of beta-catenin attenuated albuminuria after ADR treatment. Electron microscopic examination showed increased podocyte foot process effacement associated with SD abnormalities in ADR-treated control mice compared to beta-catenin-deficient mice.

Conclusions: These results show that beta-catenin in podocytes is dispensable for adult mice, but appears to be important in modulating the SD during ADR-induced perturbation of the filtration barrier.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albuminuria / chemically induced*
  • Albuminuria / physiopathology
  • Albuminuria / prevention & control*
  • Animals
  • Antibiotics, Antineoplastic / adverse effects*
  • Antibiotics, Antineoplastic / pharmacology
  • Cadherins / metabolism
  • Disease Models, Animal
  • Doxorubicin / adverse effects*
  • Doxorubicin / pharmacology
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / metabolism
  • Kidney Glomerulus / physiopathology*
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Transgenic
  • Phenotype
  • Podocytes / drug effects
  • Podocytes / metabolism
  • beta Catenin / genetics
  • beta Catenin / physiology*


  • Antibiotics, Antineoplastic
  • Cadherins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • NPHS2 protein
  • beta Catenin
  • nephrin
  • Doxorubicin