High level expression of active human alpha-1-antitrypsin in the milk of transgenic sheep.
We describe the generation of five sheep transgenic for a fusion of the ovine beta-lactoglobulin gene promotor to the human alpha 1-antitrypsin (h alpha 1AT) genomic sequences. Four of these animals are female and one male. Analysis of the expression of h alpha 1AT in the milk of three of these females shows that all express the human protein at levels greater than 1 gram per liter. In one case initial levels exceeded 60 grams per liter and stabilized at approximately 35 grams per liter as lactation progressed. Human alpha 1AT purified from the milk of these animals appears to be fully N-glycosylated and has a biological activity indistinguishable from human plasma-derived material.
Wright
G
G
Pharmaceutical Proteins Limited, Edinburgh, United Kingdom.
Carver
A
A
Cottom
D
D
Reeves
D
D
Scott
A
A
Simons
P
P
Wilmut
I
I
Garner
I
I
Colman
A
A
D000818:Animals; D030801:Animals, Genetically Modified; D015139:Blotting, Southern; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D006031:Glycosylation; D006801:Humans; D007774:Lactation; D007782:Lactoglobulins / Q000235:genetics; D008297:Male; D008892:Milk / Q000737:chemistry*; D008970:Molecular Weight; D011401:Promoter Regions, Genetic; D012756:Sheep; D014357:Trypsin / Q000378:metabolism; D000515:alpha 1-Antitrypsin / Q000032:analysis / Q000235:genetics* / Q000494:pharmacology
D007782:Lactoglobulins; D000515:alpha 1-Antitrypsin; D004247:DNA; D014357:Trypsin