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Unintended Effects of Genetic Manipulation
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Transgenic sheep had unusually high morbidity and expressed a milk-specific protein in their spleen, liver, and other organs.

Manipulated Organism: (Ovis aries).

Inserted Transgenes: Mouse genomic DNA containing the gene for whey acidic protein (WAP).

Goal of These Studies: Investigate the feasibility of using mouse WAP regulatory sequences to produce transgenic proteins in the milk of sheep.

Results of This Study:
  • Two hundred eighty eggs were recovered from bred sheep, injected with the transgenic DNA, and re-implanted in 118 sheep. Twenty-nine sheep maintained their pregnancies, giving birth to 29 lambs, 3 of which died on the first day, and 2 of which tested positive for the WAP transgene (both were female).

  • The two WAP-transgenic ewes were bred and gave birth to lambs. Both ewes produced the WAP protein in their milk, as intended.

  • According to the authors, "There was an unusually high morbidity rate in this study" (p. 71). One of the transgenic ewes had two pregnancies before dying in her third pregnancy, and both of her offspring died in the first year of life. The other transgenic ewe had one successful pregnancy before dying in her second pregnancy.

  • Although WAP gene expression in mice is highly specific to the mammary gland, substantial levels of WAP RNA were detected in many tissues of one transgenic ewe during her autopsy, including her spleen, liver, lung, kidney, and heart. The authors suggest this unintended effect could be responsible for the high morbidity rate.

Source: Wall, R. J., C. E. Rexroad, Jr., A. Powell, A. Shamay et al. (1996). "Synthesis and Secretion of the Mouse Whey Acidic Protein in Transgenic Sheep," Transgenic Research vol. 5, pp. 67-72.

Author Affiliations: USDA Agricultural Research Service, Maryland; National Institutes of Health, Maryland.

Funding: Not mentioned.

Product Status: Not on the market as of 2009.

Copyright 2009 The Nature Institute.

This document: http://natureinstitute.org/nontarget/reports/sheep_002.php

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