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, Virginia Polytechnic Institute and State University
Raymond L. Page, Virginia Polytechnic Institute and State University
Christopher G. Russell, Virginia Polytechnic Institute and State University
Anuradha Subramanian, University of Nebraska - LincolnFollow
Tracy D. Wilkins, Virginia Polytechnic Institute and State University
Francis C. Gwazdauskas, Virginia Polytechnic Institute and State University
Christoph Pittius, The American Red Cross, Rockville, MD
William N. Drohan, The American Red Cross, Rockville, MD

Date of this Version

12-15-1992

Comments

Published in Proceedings of the National Academy of Sciences of the United States of America, Vol. 89 (December 15, 1992), pp. 12003-12007. Copyright © 1992 National Academy of Sciences. Used by permission.

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 γ-carboxylation can occur at high levels in the mammary gland of a pig.