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A Transgenic MMTV-Flippase Mouse Line for Molecular Engineering in Mammary Gland and Breast Cancer Mouse Models

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Abstract

Genetically engineered mouse models have become an indispensable tool for breast cancer research. Combination of multiple site-specific recombination systems such as Cre/loxP and Flippase (Flp)/Frt allows for engineering of sophisticated, multi-layered conditional mouse models. Here, we report the generation and characterization of a novel transgenic mouse line expressing a mouse codon-optimized Flp under the control of the mouse mammary tumor virus (MMTV) promoter. These mice show robust Flp-mediated recombination in luminal mammary gland and breast cancer cells but no Flp activity in non-mammary tissues, with the exception of limited activity in salivary glands. These mice provide a unique tool for studying mammary gland biology and carcinogenesis in mice.

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Abbreviations

MMTV:

Mouse mammary tumor virus

Flp:

Flippase

Flpo:

mouse codon usage-optimized Flp

CK:

cytokeratin

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Acknowledgments

We thank P. Lorentz for support with microscopy and H. Antoniadis and U. Schmieder for technical support. We are grateful to S. Dymecki and N. Hynes for providing mice and P. Soriano and K. Alitalo for plasmids. R.B. was supported by a MD-PhD fellowship of the Swiss National Science Foundation and Swiss Cancer League. The work was supported by the Swiss National Science Foundation and the Swiss Cancer League.

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Author notes

  1. Andrea Vettiger

    Present address: Focal Area Infection Biology, Biozentrum University of Basel, Klingelbergstrasse 50/70, 4056, Basel, Switzerland

Authors and Affiliations

  1. Department of Biomedicine, University of Basel, Mattenstrasse 28, 4058, Basel, Switzerland

    Fabiana Lüönd, Ruben Bill, Andrea Vettiger & Gerhard Christofori

  2. Center for Transgenic Models, University of Basel, Mattenstrasse 22, 4058, Basel, Switzerland

    Heide Oller & Pawel Pelczar

Authors
  1. Fabiana Lüönd
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  2. Ruben Bill
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  3. Andrea Vettiger
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  4. Heide Oller
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  5. Pawel Pelczar
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  6. Gerhard Christofori
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Contributions

F.L. designed and performed the experiments, analysed the data and wrote the manuscript. R.B. conceived the idea and designed some of the experiments and analysed the data. A.V. performed some of the experiments. H.O. and P.P. performed the pronuclei microinjections. G.C. supervised the project, designed the experiments, analysed the data and wrote the manuscript.

Corresponding author

Correspondence to Gerhard Christofori.

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Conflicts of Interest

The authors declare no financial and non-financial competing interests.

Ethical Approval

All animal experiments were carried out in accordance with the guidelines of the Swiss Federal Veterinary Office (SFVO) and the Cantonal Veterinary Office of Basel-Stadt (license numbers 1878, 1023G1).

Informed Consent

No individual person’s data has been used in this project.

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Lüönd, F., Bill, R., Vettiger, A. et al. A Transgenic MMTV-Flippase Mouse Line for Molecular Engineering in Mammary Gland and Breast Cancer Mouse Models. J Mammary Gland Biol Neoplasia 24, 39–45 (2019). https://doi.org/10.1007/s10911-018-9412-4

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  • DOI: https://doi.org/10.1007/s10911-018-9412-4

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