HIGH-LEVEL SALIVARY-GLAND EXPRESSION IN TRANSGENIC MICE

A 7.1 kb mini-gene construct containing cloned DNA from the murine par otid secretory protein (PSP) gene with 6.2 kb of the promoter, has pre viously been shown to direct specific mRNA expression to the salivary glands in transgenic mice. However, the level of transgene expression in the parotid gland was only a few percent of the endogenous level. T his indicated that elements necessary for high-level expression are st ill to be found. In this study, we have searched for such regulatory e lements in additional flanking regions by using a 25 kb cloned Psp(b) fragment containing the complete structural gene, 11.4 kb of 5'-flanki ng sequence, and 2.5 kb 5'-flanking sequence as a transgene. To distin guish the expression of the transgene from that of the endogenous gene , we took advantage of an allelic difference, using an oligonucleotide that recognized the mRNA from Psp(b) and the transgene but not that f rom the other allele, Psp(a). The expression of the transgene was exam ined in animals homozygous for Psp(a). Three independent integrations all exhibited a level of parotid-gland-specific expression that corres ponded to that of the endogenous gene. Thus, sequences responsible for this high-level PSP mRNA expression are situated within the genomic D NA of the transgene.