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Characterization of the Mouse Beta Defensin 1, Defb1, Mutant Mouse Model

MRC Human Genetics Unit, Western General Hospital, Edinburgh, EH4 2XU, Scotland,¹ B.C. Research Institute for Child and Family Health, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada²

Received 17 December 2001/ Returned for modification 15 February 2002/ Accepted 11 March 2002

Beta defensins are small cationic antimicrobial peptides present in the respiratory system which have been proposed to be dysfunctional in the environment of the cystic fibrosis lung. Defb1, a murine homologue to the human beta defensins, has also been found to be expressed in the respiratory system and, in order to examine the function of beta defensins in vivo, gene targeting was used to generate Defb1-deficient (Defb1^tm1Hgu/Defb1^tm1Hgu [Defb1^-/-]) mice. The Defb1 synthetic peptide was shown to have a salt-sensitive antimicrobial activity that was stronger against Staphylococcus aureus than against Escherichia coli or Pseudomonas aeruginosa. Defb1^-/- mice were found, however, to be effective in the clearance of the cystic fibrosis relevant pathogen S. aureus from the airways after nebulization. Although no overt deleterious phenotype was evident in the Defb1^-/- mice, the number of mutant mice found to harbor bacteria of the Staphylococcus species in the bladder was significantly higher (P = 0.008) than that of controls, suggesting a role for these peptides in resistance to urinary tract infection.

Editor: E. I. Tuomanen

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