Longitudinal analysis of mammogenesis using a novel tetracycline-inducible mouse model and in vivo imaging.
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.
Creamer
Bradley A
BA
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, Nebraska 68198-6805, USA.
Triplett
Aleata A
AA
Wagner
Kay-Uwe
KU
D000818:Animals; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D007774:Lactation; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008163:Luminescent Measurements / Q000379:methods; D008321:Mammary Glands, Animal / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008894:Milk Proteins / Q000235:genetics / Q000378:metabolism*; D023421:Models, Animal; D009024:Morphogenesis; D011247:Pregnancy; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013752:Tetracycline / Q000494:pharmacology
D008894:Milk Proteins; D011993:Recombinant Fusion Proteins; C024471:whey acidic proteins; D049452:Green Fluorescent Proteins; D008156:Luciferases; D013752:Tetracycline