Comparison of the regulation of the whey acidic protein gene with that of a hybrid gene containing the whey acidic protein gene promoter in transgenic mice.

The developmentally and hormonally regulated expression of the mouse whey acidic protein (WAP) gene and a hybrid gene containing the WAP gene promoter and a cDNA for human tissue plasminogen activator (tPA) were studied in a line of transgenic mice. During mammary gland development from the mature virgin state to the seventh day of lactation, the relative concentration of WAP mRNA increased about 10(4)-fold, the increase being most pronounced between days 14 and 16 of gestation. In mammary gland organ culture from virgin and midpregnant animals, the concerted actions of insulin, hydrocortisone, and PRL were required to increase WAP mRNA levels. Steady state levels of transcripts from the WAP-tPA hybrid gene increased about 100-fold during pregnancy; this occurred mainly around day 10 of gestation. Insulin, hydrocortisone, and PRL were necessary to maintain the levels of WAP-tPA RNA in explants from virgin and pregnant animals, but could not further elevate it. The results suggest that the WAP gene promoter and upstream region contains some, but perhaps not all elements conferring developmental and hormone regulated expression of the mouse WAP gene.