THE RAT PROBASIN GENE PROMOTER DIRECTS HORMONALLY AND DEVELOPMENTALLY-REGULATED EXPRESSION OF A HETEROLOGOUS GENE SPECIFICALLY TO THE PROSTATE IN TRANSGENIC MICE

An expression cassette carrying 426 basepairs of the rat probasin (PB) gene promoter and 28 basepairs of 5'-untranslated region is sufficien t to target the expression of the bacterial chloramphenicol acetyltran sferase (CAT) gene specifically to the prostate in transgenic mice. Th e PB-CAT transgene was expressed in three of five (60%) independent li nes of mice, and this expression, as reported previously for the endog enous rat gene, was male specific, restricted primarily to the lateral , dorsal, and ventral lobes of the prostate, with only very low levels of CAT activity detected in the anterior prostate and seminal vesicle s. The developmental and hormonal regulation of the transgene also par alleled that reported for the rat gene, with a 70-fold increase in CAT activity in the mouse prostate observed between 2-7 weeks of age, a t ime corresponding to sexual maturation. PB-CAT activity in the prostat e declined after castration to 3.5% of the precastration level, and th e CAT activity in castrated males approached precastration levels when mice were supplemented with testosterone. Transgene expression in cas trated males was not induced by dexamethasone. Coinjection of PB-CAT w ith a chicken lysozyme gene matrix attachment region resulted in their cointegration and further restricted the pattern of PB-CAT to the dor solateral prostate, with suppressed expression observed in the ventral prostate. These studies demonstrate that a minimal rat probasin promo ter can target heterologous gene expression specifically to the prosta te in a developmentally and hormonally regulated fashion.