Position‐independent and high‐level expression of human α‐lactalbumin in the milk of transgenic rats carrying a 210‐kb YAC DNA

The level of expression of transgenes in transgenic animals varies among lines, and is often much lower than that of endogenous genes (position effects). In order to surmount position effects and establish a more efficient production system of transgenic animals producing pharmaceutical proteins in their milk, transgenic rats carrying 210-kb YAC DNA containing the human α-lactalbumin gene were produced. Three transgenic lines transmitted the transgene to the next generation. They had one copy of the α-lactalbumin gene and secreted human α-lactalbumin in their milk at concentrations of 2.0-4.3 mg/ml. No position effect was seen. The transgene was expressed specifically in the mammary gland of the transgenic rats. The 210-kb region is thought to contain all the DNA elements required for proper expression of the human α-lactalbumin gene. The YAC carrying the human α-lactalbumin gene is a potential vector for the expression of foreign genes in the mammary gland.