SECRETORY PROTEINS COMPETE FOR PRODUCTION IN THE MAMMARY-GLAND OF TRANSGENIC MICE

To explore the possibility that genes might compete for expression, we have studied transgenic mice producing high levels of the sheep milk protein, beta-lactoglobulin (BLG), in the mammary gland. Mice carrying one or more transgene loci expressed BLG in milk at levels ranging fr om 7 to 33 mg/ml. The effects of BLG synthesis on the levels of endoge nous milk gene expression were examined. No significant increase in to tal milk protein concentration was recorded even in mice expressing th e largest amounts of BLG. Measurement of individual milk proteins show ed that transgene protein was manufactured at the expense of host prot ein synthesized in the gland. Whey acidic protein production was more suppressed than casein production. Suppression of endogenous proteins was matched by a reduction in the corresponding steady-state mRNA leve ls; in double-transgenic mice, which expressed the largest amounts of BLG, beta-casein and whey acidic protein mRNA populations were reduced to 75 and 56% of control levels respectively. We demonstrate that an exogenous gene competes effectively for expression with endogenous gen es, Possible mechanisms of competition are discussed.