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

Milena Traykova-Brauch, Kai Schönig, Oliver Greiner, Tewfik Miloud, Anna Jauch, Manja Bode, Dean W. Felsher, Adam B. Glick, David J. Kwiatkowski, Hermann Bujard, Jürgen Horst, Magnus Von Knebel Doeberitz, Felix K. Niggli, Wilhelm Kriz, Hermann Josef Gröne, Robert Koesters

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Abstract

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-β1 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.

Original languageEnglish (US)
Pages (from-to)979-984
Number of pages6
JournalNature Medicine
Volume14
Issue number9
DOIs
Publication statusPublished - Sep 1 2008

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All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Traykova-Brauch, M., Schönig, K., Greiner, O., Miloud, T., Jauch, A., Bode, M., ... Koesters, R. (2008). An efficient and versatile system for acute and chronic modulation of renal tubular function in transgenic mice. Nature Medicine, 14(9), 979-984. https://doi.org/10.1038/nm.1865