SYNTHESIS AND SECRETION OF HUMAN SERUM-ALBUMIN BY MAMMARY-GLAND EXPLANTS OF VIRGIN AND LACTATING TRANSGENIC MICE

Transgenic mice were produced, carrying hybrid genes comprised of the ovine beta-lactoglobulin (BLG) milk protein gene promoter and human se rum albumin (HSA) coding sequences. In situ hybridization revealed hig h levels of BLG/HSA hybrid mRNA, confined to the epithelial cells of t he lactating mammary gland with a several hundred fold lower concentra tion in virgin mammary glands. During the first 24 h in culture, excep tionally high levels of HSA were secreted from explants of virgin mice , independent of hormonal control. HSA secretion was reduced considera bly during subsequent days in culture and became dependent on the pres ence of insulin, hydrocortisone and prolactin. This temporal and hormo nal pattern of regulation of HSA was different than that found for the secretion of caseins. In contrast to the vast difference in the mRNA content, the amount of HSA secreted from explants derived from lactati ng mice during the first 24 h in culture was only 2- to 5-fold higher than that found with explants from virgin transgenic mice, suggesting post-transcriptional control of HSA synthesis. The high-level synthesi s and secretion of HSA in mammary explants of lactating mice was also dependent on the presence of insulin, hydrocortisone and prolactin. Th is study confirms previous suggestion that mammary explants from virgi n transgenics may serve as a powerful tool for screening the potential of transgenic animals to secrete foreign proteins in their milk.