Bovine alpha S1-casein gene sequences direct high level expression of active human urokinase in mouse milk.
We have produced a line of transgenic mice carrying a hybrid bovine alpha S1 casein/human urokinase gene. Bovine alpha S1-casein gene regulatory sequences specifically direct expression of the human urokinase gene in lactating mammary tissue from these mice. Urokinase is a 54 kD protein with 9 disulfide bonds that is normally synthesized in the kidney; however, the casein/urokinase transgenic mice secrete active human urokinase into their milk at concentrations of 1-2 mg/ml. The mice show no other abnormalities. They give birth to, and nurse, normal sized healthy litters. Thus it is possible to produce high concentrations of a large, cysteine rich, non-milk protein in the milk of transgenic animals. This line of transgenic mice provides a model for the eventual production of transgenic farm animals producing high levels of recombinant proteins in their milk.
Biogen Inc., Cambridge, MA 02142.
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H
Meade
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Gates
E
E
Lacy
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Lonberg
D000818:Animals; D001483:Base Sequence; D002364:Caseins / Q000235:genetics*; D002417:Cattle; D005786:Gene Expression Regulation / Q000235:genetics*; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008892:Milk / Q000378:metabolism*; D008894:Milk Proteins / Q000096:biosynthesis; D008957:Models, Genetic; D008969:Molecular Sequence Data; D012313:RNA / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D015183:Restriction Mapping; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics
D002364:Caseins; D008894:Milk Proteins; D011993:Recombinant Fusion Proteins; D012313:RNA; D014568:Urokinase-Type Plasminogen Activator