Co-Authors:
Barash, I., Institute of Animal Science, Agricultural Research Organization, Volcani Center, Bet Dagan, Israel, Institute of Animal Science, Agricultural Research Organization, Volcani Center, Bet Dagan 50250, Israel
Faerman, A., Institute of Animal Science, Agricultural Research Organization, Volcani Center, Bet Dagan, Israel
Richenstein, M., Institute of Animal Science, Agricultural Research Organization, Volcani Center, Bet Dagan, Israel
Kari, R., Institute of Animal Science, Agricultural Research Organization, Volcani Center, Bet Dagan, Israel
Damary, G.-M., Institute of Animal Science, Agricultural Research Organization, Volcani Center, Bet Dagan, Israel
Shani, M., Institute of Animal Science, Agricultural Research Organization, Volcani Center, Bet Dagan, Israel
Bissell, M.J., Life Science Division, Lawrence Berkeley Laboratories, Berkeley, CA, United States
Abstract:
The expression pattern of human serum albumin (HSA) in transgenic mice carrying various HSA genomic sequences driven either by the mouse whey acidic protein (WAP) or the sheep β-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 determined in both sets of mice (~25% secreting >0.1 mg/ml), the highest level of HSA secreted into the milk in the WAP/HSA transgenic lines was one order of magnitude lower than in the BLG/HSA lines. Despite this difference, the HSA expression patterns in the mammary gland were similar and consisted of two levels of variegated expression. Studies using mammary explant cultures revealed a comparable responsiveness to the lactogenic hormones insulin, hydrocortisone, and prolactin, although the WAP/HSA gene constructs were more sensitive to the hydrocortisone effect than were the BLG/HSA vectors. When HSA vectors were stably transfected into the mouse mammary cell line CID-9, they displayed a hierarchy of expression, dependent upon the specific complement of HSA introns included. Nevertheless, the expression of HSA in four out of five WAP/HSA constructs was similar to their BLG/HSA counterparts. This construct-dependent, and promoter-independent, hierarchy was also found following transfection into the newly established Golda-1 ovine mammary epithelial cell line.