Gene expression in the mammary glands of transgenic animals.

The gene encoding the milk protein beta-lactoglobulin in sheep is expressed in the mammary gland in a tissue-specific manner during pregnancy and lactation. The unmodified sheep gene behaves appropriately in transgenic mice, and we have shown that many of the cis-acting elements that mediate this pattern of expression are located in the proximal 400 bp of the promotor. Using a combination of approaches we have identified a number of discrete cis-acting elements and their corresponding trans-acting factors that control the responsiveness of this gene in vivo. The beta-lactoglobulin promoter elements can be used to target the expression of foreign genes to the mammary gland in transgenic mice. We have used this approach in basic studies of mammary gland biology and for the production of therapeutic proteins in the milk of transgenic animals. In these circumstances, however, the promoter rarely functions optimally, and it may even be silenced; consequently, we have had to develop a number of strategies to overcome this problem. Nevertheless, foreign proteins do appear to be appropriately post-translationally modified when they are expressed in the mammary gland.