TY - JOUR
T1 - An efficient and versatile system for acute and chronic modulation of renal tubular function in transgenic mice
AU - Traykova-Brauch, Milena
AU - Schönig, Kai
AU - Greiner, Oliver
AU - Miloud, Tewfik
AU - Jauch, Anna
AU - Bode, Manja
AU - Felsher, Dean W.
AU - Glick, Adam B.
AU - Kwiatkowski, David J.
AU - Bujard, Hermann
AU - Horst, Jürgen
AU - Von Knebel Doeberitz, Magnus
AU - Niggli, Felix K.
AU - Kriz, Wilhelm
AU - Gröne, Hermann Josef
AU - Koesters, Robert
N1 - Funding Information:
This work was supported by Deutsche Forschungsgemeinschaft grants FOR406 (to W.K. and R.K.) and SFB 405 B10 (to H.-J.G.), by Schweizerische Forschungsstiftung Kind und Krebs (O.G.), by Prof. Dr. Karl und Gerhard Schiller-Stiftung (W.K.) and by US National Institutes of Health grants R01-CA85610, R01-CA105102, 3R01CA089305-03S1, NIH/NCI ICMIC P50 and NIH/NCI 1P20 CA112973 (D.W.F.). We thank P. Soriano (Fred Hutchinson Cancer Research Center) for providing Rosa26R mice; F. Zimmermann and S. Dlugosz for DNA microinjection; I. Voehringer, J. Charon-Alvarez, H. Hosser and B. Hahnel for technical assistance; the teams of the animal facilities at Deutsches Krebsforschungszentrum and Interfakultäre Biomedizinische Forschungseinrichtung Heidelberg for animal caretaking; T.P. Sijmonsma for skillful and expert handling of the mice; S. Wang for help with tissue preservation; M. Schorpp-Kistner and C. Gebhardt for expert advice in mouse embryology; R. Nonnenmacher for graphical work; and W.A. Grandy for carefully reading the manuscript.
PY - 2008/9
Y1 - 2008/9
N2 - 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.
AB - 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.
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U2 - 10.1038/nm.1865
DO - 10.1038/nm.1865
M3 - Article
C2 - 18724376
AN - SCOPUS:51349104757
SN - 1078-8956
VL - 14
SP - 979
EP - 984
JO - Nature Medicine
JF - Nature Medicine
IS - 9
ER -