TRANSGENIC MICE CARRYING AN IMBALANCE IN THE NATIVE RATIO OF A-FORM TO B-FORM OF PROGESTERONE-RECEPTOR EXHIBIT DEVELOPMENTAL ABNORMALITIES IN MAMMARY-GLANDS

In this report we document the creation of transgenic mice in which th e native ratio of A and B forms of progesterone receptor (PR) has been altered by the introduction of additional A form as transgene. We als o show that in these mice there is an aberration in mammary developmen t. In ovariectomized prepubertal PR-A transgenic mice, end buds with u nusual morphology persist after ovariectomy, and in young adult nonova riectomized mice, mammary glands have extensive lateral branching, The glands of adult mice also exhibit ductal hyperplasia with a disorgani zed basement membrane and decreased cell-cell adhesion, features commo nly associated with neoplasia, Because progesterone is a mitogenic hor mone in mammary glands and PR is required for mammary development, the se data provide direct evidence that in vivo a regulated expression of the two isoforms of PR is critical for appropriate cellular response to progesterone and that for mammary glands this may have major implic ations to carcinogenesis.