Production of Human Tissue Plasminogen Activator in Transgenic Mouse Milk

We set out to express an exogenous gene in the mammary epithelium of transgenic mice in the hope that the encoded protein would be secreted into milk. The promoter and upstream regulatory sequences from the murine whey acid protein (WAP) gene were fused to cDNA encoding human tissue plasminogen activator (t–PA) with its endogenous secretion signal sequence. This hybrid gene was injected into mouse embryos, resultant transgenic mice were mated, and milk obtained from lactating females was shown to contain biologically active t–PA. This result establishes the feasibility of secretion into the milk of transgenic animals for production of biologically active heterologous proteins, and may provide a powerful method to produce such proteins on a large scale.