THE BLADDER AS A BIOREACTOR - UROTHELIUM PRODUCTION AND SECRETION OF GROWTH-HORMONE INTO URINE

Uroplakin genes are expressed in a bladder-specific and differentiatio n-dependent fashion. Using a 3.6-kb promoter of mouse uroplakin II gen e, we have generated transgenic mice that express human growth hormone (hGH) in their bladder epithelium, resulting in its secretion into th e urine at 100-500 ng/ml. The levels of urine hGH concentration remain constant for longer than 8 months. hGH is present as aggregates mostl y in the uroplakin-delivering cytoplasmic vesicles that are targeted t o fuse with the apical surface. Using the bladder as a bioreactor offe rs unique advantages, including the utility of all animals throughout their lives. Using urine, which contains little protein and lipid, as a starting material facilitates recombinant protein purification.