Humanization of the Mouse Mammary Gland

  • A. Wronski
  • L. M. Arendt
  • Charlotte KuperwasserEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1293)


Although mouse models have provided invaluable information on the mechanisms of mammary gland development, anatomical and developmental differences between human and mice limit full understanding of this fundamental process. Humanization of the mouse mammary gland by injecting immortalized human breast stromal cells into the cleared murine mammary fat pad enables the growth and development of human mammary epithelial cells or tissue. This facilitates the characterization of human mammary gland development or tumorigenesis by utilizing the mouse mammary fat pad. Here we describe the process of isolating human mammary stromal and epithelial cells as well as their introduction into the mammary fat pads of immunocompromised mice.

Key words

Human-in-mouse model Humanization Human mammary epithelial cells Stroma Mammary gland Mammary gland biology 


  1. 1.
    Hennighausen L, Robinson GW (2005) Information networks in the mammary gland. Nat Rev Mol Cell Biol 6(9):715–725PubMedCrossRefGoogle Scholar
  2. 2.
    Smith BA, Welm AL, Welm BE (2012) On the shoulders of giants: a historical perspective of unique experimental methods in mammary gland research. Semin Cell Dev Biol 23(5):583–590, Scholar
  3. 3.
    Gusterson BA, Stein T (2012) Human breast development. Semin Cell Dev Biol 23(5):567–573, Scholar
  4. 4.
    Parmar H, Cunha GR (2004) Epithelial-stromal interactions in the mouse and human mammary gland in vivo. Endocr Relat Cancer 11(3):437–458PubMedCrossRefGoogle Scholar
  5. 5.
    Sheffield LG, Welsch CW (1988) Transplantation of human breast epithelia to mammary-gland-free fat-pads of athymic nude mice: influence of mammotrophic hormones on growth of breast epithelia. Int J Cancer 41(5):713–719PubMedCrossRefGoogle Scholar
  6. 6.
    Outzen HC, Custer RP (1975) Growth of human normal and neoplastic mammary tissues in the cleared mammary fat pad of the nude mouse. J Natl Cancer Inst 55(6):1461–1466PubMedGoogle Scholar
  7. 7.
    Kuperwasser C, Chavarria T, Wu M, Magrane G, Gray JW, Carey L, Richardson A, Weinberg RA (2004) Reconstruction of functionally normal and malignant human breast tissues in mice. Proc Natl Acad Sci U S A 101(14):4966–4971. doi: 10.1073/pnas.0401064101 PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Keller PJ, Arendt LM, Skibinski A, Logvinenko T, Klebba I, Dong S, Smith AE, Prat A, Perou CM, Gilmore H, Schnitt S, Naber SP, Garlick JA, Kuperwasser C (2012) Defining the cellular precursors to human breast cancer. Proc Natl Acad Sci U S A 109(8):2772–2777. doi: 10.1073/pnas.1017626108 PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Proia TA, Keller PJ, Gupta PB, Klebba I, Jones AD, Sedic M, Gilmore H, Tung N, Naber SP, Schnitt S, Lander ES, Kuperwasser C (2011) Genetic predisposition directs breast cancer phenotype by dictating progenitor cell fate. Cell Stem Cell 8(2):149–163. doi: 10.1016/j.stem.2010.12.007 PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Proia DA, Kuperwasser C (2006) Reconstruction of human mammary tissues in a mouse model. Nat Protoc 1(1):206–214PubMedCrossRefGoogle Scholar
  11. 11.
    Arendt LM, Rudnick JA, Keller PJ, Kuperwasser C (2010) Stroma in breast development and disease. Semin Cell Dev Biol 21(1):11–18. doi: 10.1016/j.semcdb.2009.10.003 PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media LLC New York 2015

Authors and Affiliations

  • A. Wronski
    • 1
    • 2
  • L. M. Arendt
    • 1
    • 2
    • 3
  • Charlotte Kuperwasser
    • 1
    • 2
    Email author
  1. 1.Developmental, Molecular, and Chemical Biology Department, Sackler School of Graduate Biomedical SciencesTufts University School of MedicineBostonUSA
  2. 2.Raymond and Beverly Sackler Laboratory for the Convergence of Biomedical, Physical and Engineering SciencesMolecular Oncology Research Institute, Tufts Medical CenterBostonUSA
  3. 3.Department of Comparative BiosciencesSchool of Veterinary Medicine, University of Wisconsin-MadisonMadisonUSA

Personalised recommendations