High-level expression of a heterologous protein in the milk of transgenic swine using the cDNA encoding human protein C.

Transgenic pigs were generated that produced human protein C in their milk at up to 1 g/liter. The gene construct was a fusion gene consisting of the cDNA for human protein C inserted into the first exon of the mouse whey acidic protein gene. These results demonstrate that the mouse whey acidic protein gene contains regulatory elements that can direct cDNA expression at high levels in the pig mammary gland. Recombinant human protein C that was produced at about 380 micrograms/ml per hr in transgenic pig milk possessed anticoagulant activity that was equivalent to that of protein C derived from human plasma. These studies provide evidence that gamma-carboxylation can occur at high levels in the mammary gland of a pig.