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Purpose: Proteus mirabilis is a common cause of urinary tract infection. We determined the role of Tamm-Horsfall protein as a host defense factor against the cystitis and pyelonephritis caused by P. mirabilis.

Materials and Methods: We generated Tamm-Horsfall protein gene knockout mice using homologous recombination. We introduced P. mirabilis transurethrally into the bladder of Tamm-Horsfall protein deficient (THP-/-) and genetically similar WT (THP / ) mice. We cultured urine to quantitate the degree of bacteriuria. We examined bladders and kidneys grossly and histomorphometrically to determine the intensity of inflammation.

Results: THP-/- mice had more severe bacteriuria and cystitis than THP / mice. THP-/- mice had more pyelonephritic abscesses than THP / mice. The severity of histological pyelonephritis on semiquantitative histomorphometric analysis appeared to be greater in THP-/- mice. The difference between the 2 groups approached but did not attain statistical significance (p = 0.053).

Conclusion: Tamm-Horsfall protein acts as a host defense factor against P. mirabilis induced urinary tract infection.

(C) 2009 by the American Urological Association, Inc.