The bladder as a bioreactor: urothelium production and secretion of growth hormone into urine.
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.
Kerr
D E
DE
Gene Evaluation and Mapping Laboratory, Agricultural Research Service, United States Department of Agriculture, Beltsville, MD 20705, USA.
Liang
F
F
Bondioli
K R
KR
Zhao
H
H
Kreibich
G
G
Wall
R J
RJ
Sun
T T
TT
D000818:Animals; D019149:Bioreactors; D015152:Blotting, Northern; D005260:Female; D005455:Fluorescent Antibody Technique; D019382:Human Growth Hormone / Q000096:biosynthesis* / Q000652:urine; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000235:genetics; D001743:Urinary Bladder; D060170:Uroplakin II; D019459:Urothelium / Q000378:metabolism* / Q000648:ultrastructure
D008565:Membrane Proteins; C554658:UPK2 protein, human; C554659:Upk2 protein, mouse; D060170:Uroplakin II; D019382:Human Growth Hormone