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Cross-contamination with tamoxifen induces transgene expression in non-exposed inducible transgenic mice
Rachael L. Brake1,3, Paul J. Simmons2 and C. Glenn Begley1,3
1Centre for Child Health Research and WAIMR, University of Western Australia,
Telethon Institute for Child Health Research, PO Box 855, West Perth WA 6872, Australia
2Peter MacCallum Cancer Centre, Locked Bag 1, A’Beckett Street, Victoria, 8006 Australia
3The current address of R.L. Brake is Department of Hematology Research and Pharmacokinetics,
Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA
Corresponding author: R.L. Brake
E-mail: [email protected]
Genet. Mol. Res. 3 (4): 456-462 (2004)
Received July 28, 2004
Accepted October 13, 2004
Published December 22, 2004

ABSTRACT. Inducible transgenic mouse models that impose a constraint on both temporal and spatial expression of a given transgene are invaluable. These animals facilitate experiments that can address the role of a specific cell or group of cells within an animal or in a particular window of time. A common approach to achieve inducibility involves the site-specific recombinase ‘Cre’, which is linked to a modified version of one of various steroid hormone-binding domains. Thus, the expression of Cre is regulated such that a functional nuclear transgene product can only be generated with the addition of an exogenous ligand. However, critical requirements of this system are that the nuclear localization of the transgene product be tightly regulated, that the dosage of the inducing agent remains consistent among experimental animals and that the transgene cassette cannot express in the absence of the inducing agent. We used the Cre ER(T2) cassette, which is regulated by the addition of the estrogen antagonist tamoxifen to determine whether cross-contamination of tamoxifen between animals housed together can be a significant source of spurious results. We found that cross-contamination of exogenous tamoxifen does occur. It occurred in all animals tested. We suggest that the mechanism of contamination is through exposure to tamoxifen in the general environment and/or to coprophagous behavior. These results have important implications for the interpretation and design of experiments that use ‘inducible’ transgenic animals.

Key words: Tamoxifen, Estrogen receptor, Inducible transgenic, Cre, Hormone-binding domain, ER(T2)

 

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