Expression of recombinant human granulocyte macrophage-colony stimulating factor (hGM-CSF) in mouse urine

We have generated transgenic mice expressing human granulocyte macrophage-c olony stimulating factor (hGM-CSF) in urine. In particular, the expression plasmid DNA containing mouse uroplakin II promoter was used to direct uroep ithelium-specific transcription of transgene. In this study, hGM-CSF transc ript was detected only in bladder uroepithelium as determined by northern b lot analysis. Furthermore, hGM-CSF protein was detected in the suprabasal l ayer of the uroepithelium and ureter by immunohistochemistry. The hGM-CSF w as secreted into urine at high level (up to 180 ng/ml), and enhanced prolif eration of hGM-CSF-dependent human acute monocyte leukemic cells, suggestin g that transgenic urine-derived hGM-CSF was bioactive. This is the first ca se of demonstrating biological activity of a cytokine produced in the urine of a transgenic animal. Our results demonstrate that bladder can be used a s a bioreactor to produce biologically important substances. In addition, i t suggests a potential application of bladder expression system to livestoc k for high-yield production of pharmaceuticals.