Recombinant Human Protein C Expression in the Milk of Transgenic Pigs and the Effect on Endogenous Milk Immunoglobulin and Transferrin Levels

Transgenic Research - Tập 10 - Trang 43-51 - 2001
Kevin E. Van Cott1, Henryk Lubon2, F.C. Gwazdauskas3, James Knight4, William N. Drohan2, William H. Velander1
1Department of Chemical Engineering, Virginia Tech, Blacksburg
2Jerome Holland Laboratories, American Red Cross, Rockville
3Department of Dairy Science, Virginia Tech, Blacksburg
4Department of Animal and Poultry Science, Virginia Tech, Blacksburg

Tóm tắt

Colostrum and milk are natural vehicles for acquiring passive immunity and are valuable tools for decreasing neonatant mortality from diarrheal disease. The effects of recombinant human protein C (rhPC) expression levels on endogenous immunoglobulin and transferrin content of the milk of different lineages of transgenic pigs were studied. The levels of rhPC in the milk ranged from 40 to 1200 μg/ml. Transgenic pigs with rhPC expression levels less than 500 μg/ml had no significant differences in milk protein composition with respect to nontransgenic pigs. A line of transgenic pigs having rhPC expression levels of 960–1200 μg/ml had two- to three-fold higher IgG, IgM, and secretory IgA concentrations compared to other transgenic and nontransgenic pig groups (P < 0.05), and four- to five-fold higher transferrin levels than nontransgenic pigs (P < 0.05). Changes in milk protein composition were not associated with mastitis or other pathologic disruption of epithelial cell junctions as indicated by normal casein and albumin levels in milk. Since IgG, IgM, secretory IgA, and transferrin are transported into the milk by transcytosis, higher levels of these proteins indicate that transcyctosis in the mammary epithelial cell was likely upregulated in pigs having high rhPC expression levels. This study is the first that shows a statistically significant example that mammary tissue specific expression of a heterologous protein can enhance endogenous phenotypic characteristics of milk.

Tài liệu tham khảo

Anonymous (1995) Points to consider in the manufacture and testing of therapeutic products for human use derived from transgenic animals, Docket No. 95D-0131. Center for Biologics Evaluation and Research, U.S. Food and Drug Administration.

Bleck G, Jimenez-Flores R and Bremel R (1993) Anomalous milk properties of transgenic mice expressing bovine beta-casein under control of the bovine alpha-lactalbumin 5′ flanking region. FASEB J 7: A812.

De Groot N, van Kuik-Romeijn P, Lee SH and de Boer HA (1999) Overexpression of the murine polymeric immunoglobulin receptor gene in the mammary gland of transgenic mice. Transgenic Res 8: 125–135.

Jenness R (1982) Interspecies comparison of milk proteins. In: Fox PF (ed.) Developments in Dairy Chemistry, Vol. 1 (pp. 87–114). Applied Science Publishers, New York.