ECTOPIC EXPRESSION OF BETA-LACTOGLOBULIN HUMAN SERUM-ALBUMIN FUSION GENES IN TRANSGENIC MICE - HORMONAL-REGULATION AND IN-SITU LOCALIZATION

We produced transgenic mice carrying the native sheep beta-lactoglobul in (BLG) or fusion genes composed of the BLG promoter and human serum albumin (HSA) minigenes. BLG was expressed exclusively in the mammary glands of the virgin and lactating transgenic mice evaluated. In contr ast, transgenic females carrying the BLG/HSA fusion constructs also ex pressed the HSA RNA ectopically in skeletal muscle, kidney, brain, spl een, salivary gland and skin. Ectopic expression of HSA RNA was detect ed only in strains that express the transgene in the mammary gland. Th ere was no obvious correlation between the level of the HSA RNA expres sed in the mammary gland and that found ectopically. In three transgen ic strains analysed, the expression of HSA RNA in kidney and skeletal muscle increased during pregnancy and lactation, whereas in the brain HSA expression decreased during lactation in one of the strains. HSA p rotein was synthesized in skeletal muscle and skin of strain #23 and i ts level was higher in lactating mice compared with virgin mice. Expre ssion of HSA was also analysed in males and was found to be more strin gently controlled than in females of the same strains. In situ hybridi zation analyses localized the expressed transgene in the skin, kidney, brain and salivary glands of various transgenic strains. Distinct str ain-specific and cell-type specific HSA expression patterns were obser ved in the skin. This is in contrast to the exclusive expression of th e HSA transgene in epithelial cells surrounding the alveoli of the mam mary gland. Taken together, these results suggest that the absence of sufficient mammary-specific regulatory elements in the BLG promoter se quences and/or the juxtaposition of the BLG promoter with the HSA codi ng sequences leads to novel tissue- and cell-specific expression in ec topic tissues of transgenic mice.