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 prot...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1992-12, Vol.89 (24), p.12003-12007
Main Authors: Velander, William H., Johnson, John L., Page, Raymond L., Russell, Christopher G., Subramanian, Anuradha, Wilkins, Tracy D., Gwazdauskas, Francis C., Pittius, Christoph, Drohan, William N.
Format: Article
Language:English
Subjects:
Animals
Animals, Genetically Modified - metabolism
Anticoagulants
Antigens
Biological and medical sciences
Biotechnology
Cloning, Molecular
Complementary DNA
Deoxyribonucleic acid
DNA
DNA - genetics
Fundamental and applied biological sciences. Psychology
Gene Expression
Genetic engineering
Genetic technics
Hogs
Humans
Lactation
Methods. Procedures. Technologies
Milk Proteins - metabolism
Multidisciplinary Sciences
Piglets
Protein C - genetics
Protein C - isolation & purification
Recombinant Proteins - isolation & purification
Recombinant Proteins - metabolism
RNA
RNA, Messenger - genetics
Science & Technology
Science & Technology - Other Topics
Swine
Transgenes
Transgenic animals
Transgenic animals and transgenic plants
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Summary: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 μg/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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.89.24.12003