Expression of a variant of human tissue-type plasminogen activator in transgenic mouse milk

To increase half life and solubility of the wild-type human tPA in vivo, a variant containing only essential K2 and P domains of wild tPA was cloned and directed expression in transgenic mice milk by bovine αs1 casein regulatory sequences. In two of the three resulting transgenic female mice, this modified tPA was expressed with the anticipated molecular weight, and maintained strong proteolytic activity, simultaneously present as a dissoluble form in the whey. The highest level in milk was about 300 IU/ml, 1000-fold higher than that in blood. A transgene-specific increase of tPA expression was observed from the first to the second lactation. More interesting, high concentration of this tPA has no obvious side-effects on lactation, indicating that it might be of large scale produced by transgenic livestock milk.