Generation of a Novel MMTV-tTA Transgenic Mouse Strain for the Targeted Expression of Genes in the Embryonic and Postnatal Mammary Gland

Kazuhito Sakamoto, Jeffrey W. Schmidt, Kay Uwe Wagner

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

We have generated a new and improved transgenic mouse strain that permits a temporally controlled expression of transgenes throughout mammary gland development. High expression of the tetracycline-regulatible transactivator (tTA) under control of the mouse mammary tumor virus long terminal repeat (MMTV-LTR) is restricted to mammary epithelial cells and the salivary gland. The novel MMTV-tTA mouse strain induces a sustained transactivation of responder transgenes, which can be swiftly suppressed through administration of doxycycline (Dox). An important characteristic of this strain is its expression in early progenitor cells of mammary gland anlagen beginning at day 13.5 of embryonic development. We show here that the MMTV-tTA can be used in combination with GFP reporter strains to visualize CK8/CK14-dual positive progenitors in newborn females and their derived basal and luminal epithelial cell lineages in adult females. Our observations suggest that the novel MMTV-tTA can be utilized to express exogenous proteins in multipotent mammary progenitors during the earliest stages of mammary gland development to assess their biological significance throughout mammogenesis. Moreover, we demonstrate that the expression of the MMTV-tTA is sustained during mammary gland tumorigenesis in female mice expressing wildtype ErbB2. This makes this strain particular valuable to target the expression of exogenous proteins into developing mammary tumors to assess their significance in biological processes, such as tumor cell growth and survival, metabolism, and metastasis.

Original languageEnglish (US)
Article numbere43778
JournalPloS one
Volume7
Issue number8
DOIs
StatePublished - Aug 31 2012

Fingerprint

Trans-Activators
Human Mammary Glands
mammary glands
Transgenic Mice
Genes
genetically modified organisms
Gene Expression
gene expression
mice
Tumors
Transgenes
transgenes
breasts
Breast
epithelial cells
Mouse mammary tumor virus
Epithelial Cells
mammary development
Biological Phenomena
doxycycline

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Generation of a Novel MMTV-tTA Transgenic Mouse Strain for the Targeted Expression of Genes in the Embryonic and Postnatal Mammary Gland. / Sakamoto, Kazuhito; Schmidt, Jeffrey W.; Wagner, Kay Uwe.

In: PloS one, Vol. 7, No. 8, e43778, 31.08.2012.

Research output: Contribution to journalArticle

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