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

Authors

William H. Velander, University of Nebraska-LincolnFollow
John L. Johnson, DEpartment of Anaerobic microbiology, Virginia Polytechnic Institute and State University, Blacksburg, VA
Raymond L. Page, DEpartment of Chemical Engineering,Virginia Polytechnic Institute and State University, Blacksburg, VA
Chritopher G. Russell, Department of Chemical EngineeringVirginia Polytechnic Institute and State University, Blacksburg, VA
Anuradha Subramanian, Department of chemical Engineering,University of Nebraska Lincoln.Follow
Tracy D. Wilkins, DEpartment of Anaerobic microbiology, Virginia Polytechnic Institute and State University, Blacksburg, VA
Francis C. Gwazdauskas, Deparment of Dairy Science, Virginia Polytechnic Institute and State University, Blacksburg, VAFollow
Christoph Pittus, 1The Holland Laboratory, The American Red Cross, Rockville, MD 20855
William N. Drohan, 1The Holland Laboratory, The American Red Cross, Rockville, MD 20855

Date of this Version

December 1992

Comments

Originally Published in Proc. National Academy of Science. USA Vol. 89, pp. 12003-12007, December 1992 Applied Biological Sciences And this article can be viewed at: http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&blobtype=pdf&artid=50686

Abstract

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 pg/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 y-carboxylation can occur at high levels in the mammary gland of a pig.