The molecular basis of mammary-specific and developmentally and hormonally regulated gene expression is being studied through analyses of the mouse whey acidic protein (WAP) gene in transgenic mice. It was shown that mammary specific elements are located within the promoter region, and that the absence of expression in early pregnancy is due to a repressor which keeps the gene inaccessible to transcription factors produced throughout pregnancy. WAP gene expression during pregnancy and lactation is predominantly regulated on a transcriptional rather than a post-transcriptional level. In continuation of establishing the mammary gland as a bioreactor, the mouse WAP gene was expressed in transgenic pigs. Expression levels of the mouse WAP gene in pigs were higher than in mice and a more accurate regulation was observed. WAP shows strong similarities with protease inhibitors, suggesting that it may have a function in addition to being a caloric nutrient. Female mice from about 25% of the lines and about 50% of the transgenic pigs failed to produce milk after parturition and exhibited a milchlos (agalactic) phenotype. Alveolar development and histological appearance of mammary tissue from post-partum milchlos mice were similar to that of glands from non-transgenic mice at mid-pregnancy. Precocious expression of WAP during pregnancy was associated with a non- functional mammary gland suggesting that WAP may play a role in mammary development.
