AN EFFICIENT EXPRESSION OF HUMAN GROWTH-HORMONE (HGH) IN THE MILK OF TRANSGENIC MICE USING RAT BETA-CASEIN HGH FUSION GENES/

In order to produce human growth hormone (hGH) in the milk of transgen ic mice, two expression vectors for hGH differing in their 3' flanking sequences were constructed by placing the genomic sequences of hGH ge ne under the control of the rat beta-casein gene promotor. The 3' flan king sequences of the expression constructs were derived from either t he hGH gene (pBCN1GH) or the rat beta-casein gene (pBCN2GH). Transgeni c lines bearing pBCN1GH expressed hGH more efficiently than those bear ing pBCN2GH in the milk (19-5500 mu g/mL vs 0.7-2 mu g/mL). In particu lar, one of the BCN1GH lines expressed hGH as much as 5500 +/- 620 mu g/mL. Northern blot analysis showed that the transgene expression was specifically confined to the mammary gland and developmentally regulat ed like the endogenous mouse beta-casein gene in the mammary gland. Ho wever, a low level of nonmammary expression was also detected with mor e sensitive assay methods. In conclusion, the rat beta-casein/hGH fusi on gene could direct an efficient production of hGH in a highly tissue -and stage-specific manner in the transgenic mice and the 3' flanking sequences of hGH gene had an important role for the efficient expressi on.