Transgenic livestock as bioreactors: Stable expression of human alpha-1-antitrypsin by a flock of sheep

We have previously described the generation of transgenic sheep expressing human alpha 1-antitrypsin (hα1, AT) in their milk. Here, we report the fidelity of transgene transmission and expression by these animals and their progeny. Transgene transmission has been demonstrated in four of six ovine lines studied. Three of these four lines have exhibited stable transmission of the transgene, whereas the fourth has produced some offspring with reduced copy numbers. Sequential lactations of founder animals has yielded very similar levels of hα1 AT protein in milk. Moreover, in one line, derived from a founder male, a flock of seven G1 ewes have yielded comparable levels of hα1 AT protein in first and second lactation milk. Two G2 ewes of this line have also produced levels of human protein equivalent to their mother. Although the inheritance of the same transgene in mice was reminiscent of the situation in sheep, stable expression was observed in only one of four lines studied. The importance of these observations to the use of transgenic livestock as bioreactors for the production of human proteins is discussed.