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Updated: Aug 27, 2026
Urinary Tract Infection in a Small Animal Model: Transurethral Catheterization of Male and Female Mice
Published on: December 1, 2017
Tamm-Horsfall protein knockout mice are more prone to urinary tract infection: rapid communication
James M Bates1, Haja Mohideen Raffi, Krishna Prasadan
1Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
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.
Insights
Tamm-Horsfall protein (THP) helps clear type 1 fimbriated E. coli from the urinary tract. THP-deficient mice showed increased bladder colonization, supporting THP's role in preventing urinary tract infections.
Area of Science:
- Urology
- Microbiology
- Immunology
Background:
- Uropathogenic Escherichia coli (E. coli) are common causes of urinary tract infections (UTIs).
- Type 1 fimbriated E. coli are linked to cystitis, while P fimbriated E. coli are associated with pyelonephritis.
- The role of Tamm-Horsfall protein (THP) in preventing UTIs is not definitively proven.
Purpose of the Study:
- To investigate the role of Tamm-Horsfall protein (THP) in the host defense against urinary tract infections.
- To determine if THP deficiency increases susceptibility to E. coli colonization in the urinary tract.
Main Methods:
- Generated THP gene knockout mice (THP-/-) using homologous recombination.
- Introduced type 1 or P fimbriated E. coli transurethrally into THP-/- and wild-type (THP+/+) mice.
- Quantified bacterial load in urine, bladder, and kidney tissues.
Main Results:
- THP-/- mice exhibited prolonged bacteriuria and increased bladder colonization by type 1 fimbriated E. coli compared to THP+/+ mice.
- No significant difference in kidney bacterial load was observed between THP-/- and THP+/+ mice when infected with P fimbriated E. coli.
Conclusions:
- Tamm-Horsfall protein (THP) acts as a soluble receptor for type 1 fimbriated E. coli.
- THP plays a crucial role in the elimination of type 1 fimbriated E. coli from the urinary tract, contributing to UTI prevention.
