Expression of human erythropoietin transgenes and of the endogenous wap gene in the mammary gland of transgenic rabbits during gestation and lactation

An understanding of the expression of transgenes in the mammary gland during gestation and lactation is crucial for the use of transgenic mammals as bioreactors. Here we describe the temporal pattern of expression of the endogenous rabbit WAP gene and human erythropoietin (hEPO) transgenes under the control of rabbit WAP promoter and 3' flanking sequences. The endogenous rabbit WAP gene was expressed throughout gestation including the day of mating, as well as during lactation in transgenic rabbits bearing a minigene;construct. In nonpregnant cycling females, WAP expression was found independent of transgenic status, however, WAP expression was not detected in non-cycling females. The significance of this new finding is not clear at present, hEPO mRNA was detected in mammary gland biopsies from pregnant transgenic rabbits only on day 28 of gestation. During lactation, transcripts were present in mammary gland biopsy samples taken on days 0, 7, 14 and 21. A sharp decline in the levels of transcripts was found for an hEPOcDNA gene construct at the end of lactation (day 28). Although the levels of hEPO were too low to allow a conclusion to be drawn regarding temporal or position-dependent expression, this finding may reflect an integration position effect.