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

Nature medicine | Sep 12, 2008

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 RIS Download

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

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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

Mouse Genome Informatics (Data, Gene Annotation)

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