A mouse model to dissect progesterone signaling in the female reproductive tract and mammary gland.

Considering the regulatory complexities of progesterone receptor (PR) action throughout the female reproductive axis and mammary gland, we generated a mouse model that enables conditional ablation of PR function in a spatiotemporal specific manner. Exon 2 of the murine PR gene was floxed to generate a conditional PR allele (PR(flox)) in mice. Crossing the PR(flox/flox) mouse with the ZP3-cre transgenic demonstrated that the PR(flox) allele recombines to a PR null allele (PR(d)). Mice homozygous for the recombined null PR allele (PR(d/d)) exhibit uterine, ovarian, and mammary gland defects that phenocopy those of our previously described PR knockout (PRKO) model. Therefore, this conditional mouse model for PR ablation represents an invaluable resource with which to further define in a developmental and/or reproductive stage-specific manner the individual and integrative roles of distinct PR populations resident in multiple progesterone-responsive target sites. (c) 2009 Wiley-Liss, Inc.