The bladder as a bioreactor: urothelium production and secretion of growth hormone into urine

Nat Biotechnol. 1998 Jan;16(1):75-9. doi: 10.1038/nbt0198-75.


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 that express human growth hormone (hGH) in their bladder epithelium, resulting in its secretion into the urine at 100-500 ng/ml. The levels of urine hGH concentration remain constant for longer than 8 months. hGH is present as aggregates mostly in the uroplakin-delivering cytoplasmic vesicles that are targeted to fuse with the apical surface. Using the bladder as a bioreactor offers 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bioreactors*
  • Blotting, Northern
  • Female
  • Fluorescent Antibody Technique
  • Human Growth Hormone / biosynthesis*
  • Human Growth Hormone / urine
  • Immunohistochemistry
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Transgenic
  • Promoter Regions, Genetic / genetics
  • Urinary Bladder*
  • Uroplakin II
  • Urothelium / metabolism*
  • Urothelium / ultrastructure


  • Membrane Proteins
  • UPK2 protein, human
  • Upk2 protein, mouse
  • Uroplakin II
  • Human Growth Hormone