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.
Traykova-Brauch
Milena
M
Department of Cellular and Molecular Pathology, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Schönig
Kai
K
Greiner
Oliver
O
Miloud
Tewfik
T
Jauch
Anna
A
Bode
Manja
M
Felsher
Dean W
DW
Glick
Adam B
AB
Kwiatkowski
David J
DJ
Bujard
Hermann
H
Horst
Jürgen
J
von Knebel Doeberitz
Magnus
M
Niggli
Felix K
FK
Kriz
Wilhelm
W
Gröne
Hermann-Josef
HJ
Koesters
Robert
R
D000818:Animals; D004195:Disease Models, Animal; D004318:Doxycycline / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D005355:Fibrosis / Q000235:genetics / Q000503:physiopathology; D007150:Immunohistochemistry; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics; D007690:Polycystic Kidney Diseases / Q000235:genetics* / Q000503:physiopathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics
D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; C499496:Pax8 protein, mouse; D015534:Trans-Activators; D053773:Transforming Growth Factor beta1; C000624651:Tsc1 protein, mouse; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins; D004318:Doxycycline