title: An efficient and versatile system for acute and chronic modulation of renal tubular function in transgenic mice.
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 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.
authors: Department of Cellular and Molecular Pathology, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors: Milena
authors: M
authors: Traykova-Brauch
authors: Kai
authors: K
authors: Schönig
authors: Oliver
authors: O
authors: Greiner
authors: Tewfik
authors: T
authors: Miloud
authors: Anna
authors: A
authors: Jauch
authors: Manja
authors: M
authors: Bode
authors: Dean W
authors: DW
authors: Felsher
authors: Adam B
authors: AB
authors: Glick
authors: David J
authors: DJ
authors: Kwiatkowski
authors: Hermann
authors: H
authors: Bujard
authors: Jürgen
authors: J
authors: Horst
authors: Magnus
authors: M
authors: von Knebel Doeberitz
authors: Felix K
authors: FK
authors: Niggli
authors: Wilhelm
authors: W
authors: Kriz
authors: Hermann-Josef
authors: HJ
authors: Gröne
authors: Robert
authors: R
authors: Koesters
mesh_terms: 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
chemical_list: 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