Gene expression in the mammary gland.

We have demonstrated that the ovine genomic clone SS1 can be used to generate transgenic mice that produce significant quantities of BLG protein in milk. The smallest BLG construct so far examined that retains the ability to direct BLG to mouse milk encompasses approximately 7.3 kb of genomic DNA, of which about 0.8 kb is derived from the promoter region. Gene expression is tissue-specific and regulated in a temporal and developmental fashion that is similar to that reported for sheep. We conclude, therefore, that the cis-acting sequences determining mammary expression of the ovine BLG gene are correctly interpreted in mice, despite the absence of an equivalent gene in this species, and that conclusions drawn from future work on BLG expression in the mammary gland of transgenic mice will be broadly applicable in sheep and other ruminant species. Work is currently in progress to define other sequences within the promoter of BLG that are required for regulated expression in transgenic mice. These and other studies into the DNA-protein interactions within the promoter which are required for efficient tissue-specific, regulated expression should lead to a greater understanding of milk protein gene expression in the mammary gland. Furthermore, in the current absence of a suitable in-vitro system, the mouse will be most useful for evaluating the expression of further constructs designed to express foreign proteins in milk of domestic ruminants.