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Title: THE BLADDER AS A BIOREACTOR: UROTHELIUM PRODUCTION AND SECRETION OF GROWTH HORMONE INTO URINE.

Author
item KERR, DAVID - UNIV. OF VERMONT
item LIANG, FENGXIA - NYU MEDICAL SCHOOL
item BONDIOLI, KENNETH - ALEXION CORP.
item ZHAO, HAIPING - NYU MEDICAL SCHOOL
item KREIBICH, GERT - NYU MEDICAL SCHOOL
item Wall, Robert
item SUN, TUNG-TIEN - NYU MEDICAL SCHOOL

Submitted to: Nature Biotechnology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/2/1997
Publication Date: N/A
Citation: N/A

Interpretive Summary: The bioreactor industry, based on producing pharmaceuticals in the milk of transgenic livestock, has realized that one of the most significant cost of production is the cost of purification of the pharmaceuticals from milk. We believe those costs could be reduced if pharmaceuticals were secreted into a less complex fluid such as urine. To test the feasibility producing pharmaceuticals in urine we have generated transgenic mice that make human growth hormone in the epithelial cells lining the inside of the bladder. In three transgenic lines studied, growth hormone was secreted into urine at a fairly constant rate over the animal's lives and offspring production was about the same as their parents. Using the bladder as a bioreactor organ has several potential advantages over the mammary gland. Urine is a much less complex solution than milk, which should reduce purification costs. Urine can be collected shortly after the animal is born, whereas milk can only be collected after females have reached sexual maturity and had an offspring and, urine can be collected from both males and females. This first report of using the bladder as a bioreactor provides an alternative approach to "pharming."

Technical Abstract: Uroplakin genes are expressed in a bladder-specific and differentiation dependent fashion. Using a 3.6-Kb promoter of mouse uroplakin II gene, we have generated transgenic mice expressing human growth hormone (hGH) in their bladder epithelium and secreting it into the urine at 100-500ng/ml. The levels of uring hGH concentration remain constant for >8 months, and is characteristic of the individual mouse lines. hGH is present as aggregates mostly in the uroplakin-delivering cytoplasmic vesicles that are targeted to fuse with the apical surface. Bladder as a bioreactor offers unique advantages including the utility of all animals throughout their lives, and the use of urine as a starting material which contain little proteins and lipids thus facilitating protein purification.