1. The molecular basis of mammary-specific and hormone regulated gene expression is being studied through analyses of regulatory elements of the mouse whey acidic protein (WAP) gene using transgenic animals. There is evidence to suggest that prolactin induces milk protein gene expression during pregnancy by a posttranscriptional mechanism. To test this, a mouse WAP gene allele, different from the endogenous one was introduced into transgenic mice and its expression was analyzed during pregnancy and upon prolactin stimulation. Whereas the endogenous WAP gene was strongly induced in the second half of pregnancy and by prolactin, expression of the transgene was considerably less affected. This suggests that induction of WAP gene expression during pregnancy and upon hormonal stimulation is mainly regulated at the transcriptional level and that the corresponding element(s) is located several kb from the promoter. In continuation of establishing the mammary gland as a bioreactor the human CD4 receptor was expressed in milk of transgenic mice. A model system for transgenic farm animals was established with altered milk protein composition. Transgenic pigs carrying the mouse WAP gene were generated and high levels of WAP were detected in milk, suggesting that it is possible to express foreign proteins in milk of transgenic dairy animals. 2. The enhancer of the immediate early 1 gene of the human cytomegalovirus contains several repeated and unique transcription elements. Since it is possible that transcription elements may interact with each other to fully activate the gene, synergism between such elements and between different signalling pathways was investigated. Specifically, NF1 and kB elements, can synergistically activate transcription in several cell types. In addition, the cAMP response element was synergistically activated by CAMP and PHA, suggesting convergence of the protein kinase A and C pathways on this transcription element.
