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Infect Immun, March 1998, p. 1225-1232, Vol. 66, No. 3
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Mouse beta -Defensin 1 Is a Salt-Sensitive Antimicrobial Peptide Present in Epithelia of the Lung and Urogenital Tract

Robert Bals, Mitchell J. Goldman, and James M. Wilson*

Department of Molecular and Cellular Engineering, The Institute for Human Gene Therapy, The University of Pennsylvania Medical Center, and The Wistar Institute, Philadelphia, Pennsylvania 19104-4268

Received 22 August 1997/Returned for modification 29 October 1997/Accepted 2 December 1997

One component of host defense at mucosal surfaces appears to be epithelium-derived peptides with antimicrobial activity called defensins. Human beta -defensin 1 (hBD-1) represents the first member of the beta -defensin family isolated from humans and has been implicated in the pathogenesis of cystic fibrosis. We describe in this report the isolation and characterization of a murine homolog of hBD-1 called mouse beta -defensin 1 (mBD-1). The predicted amino acid sequence shows the hallmark features of other known epithelial beta -defensins, including the ordered array of six cysteine residues. Analysis of a genomic clone of mBD-1 revealed two exons separated by a 15-kb intron. By use of fluorescence in situ hybridization, the mBD-1 gene was localized at the proximal portion of chromosome 8, the site where mouse alpha -defensins are found. Lysates from cells transfected with the mBD-1 cDNA showed antibacterial activity against gram-positive and gram-negative bacteria. mBD-1 transcripts were found in kidney, liver, and female reproductive organ tissues. In the airways, mBD-1 is expressed diffusely throughout the epithelial cells of the large proximal airways with less expression in the small distal airways and no expression in alveolar cells. The present study demonstrates that a beta -defensin potentially homologous to human beta -defensin 1 is present in the respiratory system and other mucosal surfaces in mice.

* Corresponding author. Mailing address: Department of Molecular and Cellular Engineering, The Institute for Human Gene Therapy, The University of Pennsylvania Medical Center, and The Wistar Institute, Room 204, 3601 Spruce Street, Philadelphia, PA 19104-4268. Phone: (215) 898-3000. Fax: (215) 898-6588. E-mail: jurmu{at}wista.wista.upenn.edu.




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