Longitudinal analysis of mammogenesis using a novel tetracycline-inducible mouse model and in vivo imaging

Authors

  • Bradley A. Creamer,

    1. Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, Nebraska
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    • B.A.C. and K.-U.W. designed research; B.A.C., A.A.T., and K.-U.W. performed research and analyzed data; B.A.C. and K.-U.W. wrote the paper.

  • Aleata A. Triplett,

    1. Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, Nebraska
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    • B.A.C. and K.-U.W. designed research; B.A.C., A.A.T., and K.-U.W. performed research and analyzed data; B.A.C. and K.-U.W. wrote the paper.

  • Kay-Uwe Wagner

    Corresponding author
    1. Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, Nebraska
    2. Department of Pathology and Microbiology, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, Nebraska
    • Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Rm. 8009, Omaha, NE 68198-6805
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    • B.A.C. and K.-U.W. designed research; B.A.C., A.A.T., and K.-U.W. performed research and analyzed data; B.A.C. and K.-U.W. wrote the paper.


  • The authors declare no conflict of interest.

Abstract

We generated a novel mouse model, which expresses the tetracycline-inducible transactivator under the regulation of the endogenous whey acidic protein gene. Using a tet-responsive luciferase reporter transgene, we demonstrated that the Wap-rtTA knockin allele allows a tightly controlled temporal and spatial expression of transgenes in the mammary gland in a ligand-inducible manner. The longitudinal analysis of individual females throughout their reproductive cycles using in vivo bioluminescence imaging confirmed that the expression of the Wap-rtTA knockin allele is highly upregulated during lactation. However, the extent of the transcriptional activation of the targeted Wap locus is dependent on the suckling stimulus and milk retrieval. In addition, we used WAP-rtTA/TetO-H2B–GFP double-transgenic females to monitor the presence of GFP-labeled parity-induced mammary epithelial cells (PI-MECs) during the postlactational involution period. The study shows that, unlike their progeny in mammary epithelial transplants as reported previously, PI-MECs themselves may not belong to the long-term label-retaining epithelial subtype. genesis 47:234–245, 2009. © 2009 Wiley-Liss, Inc.

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