EXPRESSION OF SYNTHETIC CDNA SEQUENCES ENCODING HUMAN INSULIN-LIKE GROWTH-FACTOR-I (IGF-1) IN THE MAMMARY-GLAND OF TRANSGENIC RABBITS

We have developed an expression system where foreign proteins are synt hesized specifically in the mammary gland of transgenic rabbits and se creted into the milk. Regulatory elements were isolated from the bovin e alpha(S1)-casein-encoding gene and combined with a synthetic DNA cod ing for human IGF-1 and for [GIn(58)]IGF-1, an IGF-1 analogue. The res ulting hybrid DNA constructs were used to generate transgenic rabbits. Females of seven transgenic lines tested were positive for synthesis of IGF-1. Transmission of the transgene to progeny and IGF-I productio n in female offspring was observed in all transgenic lines analysed. A s expected, expression of transgene mRNA could only be detected in the mammary gland. Production levels of transgenic protein were as high a s 1 g IGF-1 per liter rabbit milk. IGF-1, as well as [Gln(58)]IGF-1, w hen secreted into rabbit milk, was correctly processed and biologicall y active. IGF-1 was purified from the milk of transgenic rabbits to a nearly homogenous active form.