Production of longer acting tissue plasminogen activator of humans in milk of transgenic mice.
An exogenous gene was expressed in the mammary epithelium of transgenic mice in the hope that the encoded protein could be secreted into milk. The transgenic mice carrying the promoter and upstream regulatory sequences from the sheep BLG gene which were fused to cDNA encoding human tissue plasminogen activator (tPA) with its endogenous secretion signal sequence were generated. The hybrid genes were microinjected into mouse embryos. Two mice were identified as being transgenic by Southern blot. Milk obtained from lactating females contained biologically active tPA, and its concentration was calculated to be about 1.5 microg/ml. This result establishes the feasibility of secreting protein into the milk of transgenic animals for production of biologically active tPA proteins, and may provide a powerful method to produce such proteins on a large scale.
Zhou
J
J
Institute of Biotechnology, Beijing, China.
Deng
J
J
Huang
P
P
Huang
C
C
D000818:Animals; D015139:Blotting, Southern; D015342:DNA Probes; D015246:Deoxyribonuclease EcoRI; D015870:Gene Expression; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008892:Milk; D010960:Plasminogen Activators / Q000096:biosynthesis / Q000235:genetics*; D012756:Sheep
D015342:DNA Probes; D015246:Deoxyribonuclease EcoRI; D010960:Plasminogen Activators