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

Genesis. 2009 Apr;47(4):234-45. doi: 10.1002/dvg.20480.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Female
  • Gene Expression Regulation, Developmental / drug effects
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Immunohistochemistry
  • Lactation
  • Luciferases / genetics
  • Luciferases / metabolism
  • Luminescent Measurements / methods
  • Mammary Glands, Animal / cytology
  • Mammary Glands, Animal / growth & development
  • Mammary Glands, Animal / metabolism*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Milk Proteins / genetics
  • Milk Proteins / metabolism*
  • Models, Animal*
  • Morphogenesis
  • Pregnancy
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tetracycline / pharmacology


  • Milk Proteins
  • Recombinant Fusion Proteins
  • whey acidic proteins
  • Green Fluorescent Proteins
  • Luciferases
  • Tetracycline