title: Generation of a novel rtTA transgenic mouse to induce time-controlled, tissue-specific alterations in Pax2-expressing cells.
abstract: The paired-box transcription factor Pax2 plays a major role in early development of the kidney and the central nervous system. It is expressed in the metanephric mesenchyme of the developing kidney, at the midbrain-hindbrain boundary and the anlagen of the inner ear. The early expression of Pax2, especially in the developing kidney, prompted us to use this locus as a novel genetic tool to introduce temporally-controlled expression of transgenes. We generated a transgenic Pax2-rtTA mouse strain through genetic recombineering using a large BAC clone which drives expression of TetO-controlled transgenes upon doxycycline treatment in natively Pax2-expressing tissues. We show that expression of a TetO-responsive lacZ gene is tightly regulated by addition of doxycycline and can be detected in all Pax2-expressing tissues. Our transgenic Pax2-rtTA mouse thus represents a suitable tool to study the cell fates and molecular pathways in Pax2-positive tissues during development, such as the kidney. We further propose that the Pax2-rtTA tool has great potential to induce time-controlled, tissue-specific alterations for tumorigenic transformation of Pax2-expressing cells for generating in vivo tumor models, such as Wilms tumor.
authors.affiliation: Department of Oncology, University Children's Hospital, Zurich, Switzerland.
authors.forename: Alexa
authors.initials: A
authors.lastname: Burger
authors.forename: Robert
authors.initials: R
authors.lastname: Koesters
authors.forename: Beat W
authors.initials: BW
authors.lastname: Schäfer
authors.forename: Felix K
authors.initials: FK
authors.lastname: Niggli
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D022202:Chromosomes, Artificial, Bacterial; D004268:DNA-Binding Proteins / Q000378:metabolism; D004318:Doxycycline / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental; D007668:Kidney / Q000196:embryology / Q000378:metabolism; D007763:Lac Operon; D051379:Mice; D008822:Mice, Transgenic; D051762:PAX2 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D019076:Transgenes
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D051762:PAX2 Transcription Factor; C497319:Pax2 protein, mouse; C083139:Tet O resistance protein, Bacteria; D004318:Doxycycline