Premium
Targeting reverse tetracycline‐dependent transactivator to murine mammary epithelial cells that express the progesterone receptor
Author(s) -
Mukherjee Atish,
Soyal Selma M.,
FernandezValdivia Rodrigo,
DeMayo Francesco J.,
Lydon John P.
Publication year - 2007
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/dvg.20336
Subject(s) - transactivation , biology , doxycycline , mammary gland , microbiology and biotechnology , cancer research , gene expression , gene , cancer , genetics , breast cancer , antibiotics
Through an established gene‐targeting strategy, reverse tetracycline‐dependent transactivator ( rtTA ) was targeted downstream of the murine progesterone receptor ( PR ) promoter. Mice were generated in which one ( PR +/ rtTA ) or both ( PR rtTA/ rtTA ) PR alleles harbor the rtTA insertion. The PR +/ rtTA and PR rtTA / rtTA knockins exhibit phenotypes identical to the normal and the progesterone receptor knockout mouse, respectively. Crossed with the TZA reporter, which carries the TetO‐LacZ responder transgene, the PR +/ rtTA / TZA and PR rtTA / rtTA / TZA bigenics exhibit doxycycline‐induced β‐galactosidase activity specifically in progesterone responsive target tissues such as the mammary gland, uterus, ovary, and pituitary gland. In the case of the PR +/ rtTA / TZA mammary epithelium, dual immunofluorescence demonstrated that PR expression and doxycycline‐induced β‐galactosidase activity colocalized; β‐galactosidase was not detected in the absence of doxycycline. Although both the PR +/ rtTA and PR rtTA / rtTA knockins represent innovative animal models with which to further query progesterone's mechanism of action in vivo, the PR rtTA / rtTA mouse in particular promises to provide unique insight into the paracrine mechanism of action, which underpins progesterone's involvement in mammary morphogenesis with obvious implications for extending our understanding of this steroid's role in breast cancer progression. genesis 45:639–646, 2007. © 2007 Wiley‐Liss, Inc.