Transgenic sheep had unusually high morbidity and expressed a
milk-specific protein in their spleen, liver, and other organs.
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.
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.
USDA Agricultural Research Service, Maryland; National Institutes of
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