| Transgenic Approaches for Modifying the Mammary Gland to Produce Therapeutic Proteins Donato Romagnolo and Richard P. DiAugustine Laboratory of Biochemical Risk Analysis, National Institute of Environmental and Health Sciences, Research Triangle Park, North Carolina 27709 USA Abstract
Bioengineering of the mammary gland to produce proteins of therapeutic and industrial value is the result of extensive investigation of the physiology of the mammary gland and the ability to generate transgenic animals. Targeting the expression of heterologous proteins to mammary tissue requires a thorough understanding of the biochemical events that coordinate growth and differentiation of the mammary gland and of the hormonal and developmental regulation of expression of milk protein genes. The characterization of mammary-specific promoter regions in milk protein genes and knowledge of the mechanisms that confer integration site-independent expression of transgenes have significantly contributed to modifying the mammary gland to produce heterologous proteins of therapeutic interest. The generation of large transgenic farm animals provides the opportunity for large-scale production of proteins in milk that have a therapeutic value but are naturally present at low concentrations in biological fluids. Transgenic mammary epithelial cells offer a versatile research model in biomedical, environmental health, and neonatal toxicology research. Key words: chronic and hereditary diseases, environmental and health research, gene expression, lactation, mammary gland, therapeutic proteins, transgenics. Environ Health Perspect 102:846-851 (1994) http://ehpnet1.niehs.nih.gov/docs/1994/102-10/romagnolo.html Address correspondence to D. Romagnolo, Laboratory of Biochemical Risk Analysis, MD4-01, NIEHS, PO Box 12233, Research Triangle Park, NC 27709 USA. We thank R.M. Akers, Virginia Polytechnic Institute and State University, K.G. Nelson, NIEHS, and B.A. Merrick, NIEHS, for critical review of the manuscript, and L.L. Wright, NIEHS, for help with the literature search. We also acknowledge F.C. Gwazdauskas, Virginia Polytechnic Institute and State University, for providing bibliographic material on human protein C and Rein Strijker, Gene Pharming Europe B.V., for communicating unpublished results on human lactoferrin. Received 23 May 1994 ; accepted 22 July 1994.
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