In vivo and in vitro expression of human serum albumin genomic sequences in mammary epithelial cells with beta-lactoglobulin and whey acidic protein promoters

The expression pattern of human serum albumin (HSA) in transgenic mice carr ying various HSA genomic sequences driven either by the mouse whey acidic p rotein (WAP) or the sheep beta-lactoglobulin (BLG) promoters, was compared. The pattern of HSA expression in both WAP/HSA and BLG/HSA transgenic lines was copy number independent, and the major site of ectopic expression was the skeletal muscle. Although an equal proportion of expressors was determi ned in both sets of mice (similar to 25% secreting >0.1 mg/ml), the highest level of HSA secreted into the milk in the WAP/HSA transgenic lines was on e order of magnitude lower than in the BLG/HSA lines. Despite this differen ce, the HSA expression patterns in the mammary gland were similar and consi sted of two levels of variegated expression. Studies using mammary explant cultures revealed a comparable responsiveness to the lactogenic hormones in sulin, hydrocortisone, and prolactin, although the WAP/HSA gene constructs were more sensitive to the hydrocortisone effect than were the BLG/HSA vect ors. When HSA vectors were stably transfected into the mouse mammary cell l ine CID-9, they displayed a hierarchy of expression, dependent upon the spe cific complement of HSA introns included. Nevertheless, the expression of H SA in four out of five WAP/HSA constructs was similar to their BLG/HSA coun terparts. This construct-dependent, and promoter-independent, hierarchy was also found following transfection into the newly established Golda-1 ovine mammary epithelial cell line. Mol. Reprod. Dev. 52.241-252, 1999. (C) 1999 Wiley-Liss, Inc.