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Generation of a novel rtTA transgenic mouse to induce time‐controlled, tissue‐specific alterations in Pax2 ‐expressing cells
Author(s) -
Burger Alexa,
Koesters Robert,
Schäfer Beat W.,
Niggli Felix K.
Publication year - 2011
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/dvg.20701
Subject(s) - biology , transgene , genetically modified mouse , microbiology and biotechnology , fate mapping , doxycycline , gene , genetics , embryonic stem cell , antibiotics
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. genesis 49:797–802, 2011. © 2011 Wiley‐Liss, Inc.