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An efficient and versatile system for acute and chronic modulation of renal tubular function in transgenic mice.

We describe a transgenic mouse line, Pax8-rtTA, which, under control of the mouse Pax8 promoter, directs high levels of expression of the reverse tetracycline-dependent transactivator (rtTA) to all proximal and distal tubules and the entire collecting duct system of both embryonic and adult kidneys. Using crosses of Pax8-rtTA mice with tetracycline-responsive c-MYC mice, we established a new, inducible model of polycystic kidney disease that can mimic adult onset and that shows progression to renal malignant disease. When targeting the expression of transforming growth factor beta-1 to the kidney, we avoided early lethality by discontinuous treatment and successfully established an inducible model of renal fibrosis. Finally, a conditional knockout of the gene encoding tuberous sclerosis complex-1 was achieved, which resulted in the early outgrowth of giant polycystic kidneys reminiscent of autosomal recessive polycystic kidney disease. These experiments establish Pax8-rtTA mice as a powerful tool for modeling renal diseases in transgenic mice.

Pubmed ID: 18724376


  • Traykova-Brauch M
  • Schönig K
  • Greiner O
  • Miloud T
  • Jauch A
  • Bode M
  • Felsher DW
  • Glick AB
  • Kwiatkowski DJ
  • Bujard H
  • Horst J
  • von Knebel Doeberitz M
  • Niggli FK
  • Kriz W
  • Gröne HJ
  • Koesters R


Nature medicine

Publication Data

September 12, 2008

Associated Grants

  • Agency: NCI NIH HHS, Id: 1P20 CA112973
  • Agency: NCI NIH HHS, Id: 3R01CA089305-03S1
  • Agency: NCI NIH HHS, Id: P01 CA120964
  • Agency: NCI NIH HHS, Id: R01-CA105102
  • Agency: NCI NIH HHS, Id: R01-CA85610

Mesh Terms

  • Animals
  • Disease Models, Animal
  • Doxycycline
  • Fibrosis
  • Immunohistochemistry
  • Kidney Tubules
  • Mice
  • Mice, Transgenic
  • Paired Box Transcription Factors
  • Polycystic Kidney Diseases
  • Promoter Regions, Genetic
  • Trans-Activators
  • Transforming Growth Factor beta1
  • Tumor Suppressor Proteins