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Tamm-Horsfall protein knockout mice are more prone to urinary tract infection: rapid communication.


BACKGROUND: Human colon contains many bacteria that commonly colonize the perineum and frequently enter the urinary tract. Uropathogenic Escherichia coli are the most common cause of urinary tract infection. Type 1 fimbriated E. coli have been associated with cystitis, and P fimbriated E. coli with pyelonephritis. Factors involved in clearing bacteria from the urinary tract are poorly understood. Tamm-Horsfall protein (THP), the most abundant protein in mammalian urine, has been postulated to play a role in defense against urinary tract infection but definitive proof for this idea has been lacking. METHODS: In this study, we generated THP gene knockout mice by the technique of homologous recombination, and examined if the THP-deficient (THP-/-) mice were more prone to urinary tract infection. Various strains of E. coli expressing type 1 or P fimbriae were introduced transurethrally into the bladders of the THP-/- and genetically similar wild-type (THP+/+) mice. Urine, bladder, and kidney tissues were obtained from the mice and cultured for bacterial growth. RESULTS: THP-/- mice inoculated with type 1 fimbriated E. coli had a longer duration of bacteriuria, and more intense colonization of the urinary bladder in comparison with THP+/+ mice. When inoculated with a P fimbriated strain of E. coli, the THP-/- mice showed no difference in kidney bacterial load when compared with the THP+/+ mice. CONCLUSION: These findings support the idea that THP serves as a soluble receptor for type 1 fimbriated E. coli and helps eliminate bacteria from the urinary tract.

Pubmed ID: 14871399


  • Bates JM
  • Raffi HM
  • Prasadan K
  • Mascarenhas R
  • Laszik Z
  • Maeda N
  • Hultgren SJ
  • Kumar S


Kidney international

Publication Data

March 11, 2004

Associated Grants


Mesh Terms

  • Animals
  • Bacteriuria
  • Escherichia coli Infections
  • Genetic Predisposition to Disease
  • Kidney
  • Mice
  • Mice, Knockout
  • Mucoproteins
  • Urinary Bladder
  • Urinary Tract Infections
  • Uromodulin