• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

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

Authors

  • 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

Journal

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