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Nucleic Acids Research, 2002, Vol. 30, No. 23 e134
© 2002 Oxford University Press

Stringent doxycycline dependent control of CRE recombinase in vivo

Kai Schönig, Frieder Schwenk1, Klaus Rajewsky1 and Hermann Bujard*

Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany and 1 Institute for Genetics, University of Cologne, Weyertal 121, D-50931 Cologne, Germany

*To whom correspondence should be addressed. Tel: +49 6221 548214; Fax: +49 6221 545892; Email: h.bujard{at}zmbh.uni-heidelberg.de
Present addresses:
Frieder Schwenk, Artemis Pharmaceuticals GmbH, Neurather Ring 1, D-51063 Cologne, Germany
Klaus Rajewsky, Center for Blood Research, Harvard University, 200 Longwood Ave, Boston, MA 02115, USA
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors

The strategy of modulating gene activities in vivo via CRE/loxP recombination would greatly profit from subjecting the recombination event to an independent and stringent temporal control. Here, we describe a transgenic mouse line, LC-1, where the expression of the cre and luciferase gene is tightly controlled by the Tet system. Using the R26R mouse line as indicator for CRE activity, and mouse lines expressing tetracycline controlled transactivators (tTA/rtTA) in various tissues, we show that; (i) in the non-induced state CRE recombinase is tightly controlled throughout the development and adulthood of an animal; (ii) upon induction, efficient recombination occurs in the adult animal in all tissues where tTA/rtTA is present, including hepatocytes, kidney cells, neurons and T lymphocytes; and (iii) no position effect appears to be caused by the LC-1 locus. Moreover, using the novel rTALAP-1 mouse line, we show that in hepatocytes, complete deletion of the loxP-flanked insert in R26R animals is achieved less than 48 h after induction. Thus, the LC-1 mouse appears suitable for exploiting two rapidly increasing collections of mouse lines of which one provides tTA/rtTA in specific cell types/tissues, and the other a variety of loxP-flanked genes.


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