Position-independent and copy-number-related expression of a goat bacterial artificial chromosome alpha-lactalbumin gene in transgenic mice

Abstract

A bacterial artificial chromosome goat insert comprising the alpha-lactalbumin-encoding transcription unit with approximately 150 and 10 kb of 5'- and 3'-flanking sequences, respectively, was micro-injected into mouse eggs. In six out of seven transgenic lines, the level of mammary tissue- and stage-specific expression was position-independent and copy-number-dependent. The exogenous alpha-lactalbumin yield, about 0.8 mg/ml of milk per copy, compared favourably with the alpha-lactalbumin content of mouse and goat milks, about 0.8 and >1 mg/ml, respectively. This suggests that the insert contains most if not all of the cis-acting elements involved in the full and specific expression of the goat alpha-lactalbumin gene and opens up opportunities to use this vector to target expression of foreign genes in the lactating mammary gland of transgenic animals. The transgene was silent in the seventh line for an unknown reason.