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Infection and Immunity, September 1999, p. 4827-4833, Vol. 67, No. 9
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Molecular Cloning and Characterization of Rat Genes
Encoding Homologues of Human
-Defensins
Hong Peng
Jia,1
Jesse N.
Mills,1
Fariba
Barahmand-Pour,2
Darryl
Nishimura,1
Rama K.
Mallampali,3
Guoshun
Wang,1
Kerry
Wiles,1
Brian F.
Tack,4
Charles L.
Bevins,2 and
Paul B.
McCray Jr.1,*
Departments of
Pediatrics,1 Internal
Medicine,3 and
Microbiology,4 University of Iowa
College of Medicine, Iowa City, Iowa, and Department of
Immunology, Lerner Research Institute, The Cleveland Clinic Foundation,
Cleveland, Ohio2
Received 10 March 1999/Returned for modification 13 April
1999/Accepted 12 May 1999
-Defensins are cationic peptides with broad-spectrum
antimicrobial activity that may play a role in mucosal defenses of
several organs. They have been isolated in several species, and in
humans, two
-defensins have been identified. Here, we report the
identification of two genes encoding
-defensin homologues in the
rat. Partial cDNAs were found by searching the expressed-sequence-tag
database, and primers were designed to generate full-length mRNA coding sequences. One gene was highly similar to the human
-defensin-1 (HBD-1) gene and mouse
-defensin-1 gene at both the nucleic acid and
amino acid levels and was termed rat
-defensin-1 (RBD-1). The other
gene, named RBD-2, was homologous to the HBD-2 and bovine tracheal
antimicrobial peptide (TAP) genes. The predicted prepropeptides were
strongly cationic, were 69 and 63 residues in length for RBD-1 and
RBD-2, respectively, and contained the six-cysteine motif
characteristic of
-defensins. The
-defensin genes mapped closely
on rat chromosome 16 and were closely linked to the
-defensins genes, suggesting that they are part of a gene cluster, similar to the
organization reported for humans. Northern blot analysis showed that
both RBD-1 and RBD-2 mRNA transcripts were ~0.5 kb in length; RBD-1
mRNA was abundantly transcribed in the rat kidney, while RBD-2 was
prevalent in the lung. Reverse transcription-PCR indicated that RBD-1
and RBD-2 mRNAs were distributed in a variety of other tissues. In the
lung, RBD-1 mRNA expression localized to the tracheal epithelium while
RBD-2 was expressed in alveolar type II cells. In conclusion, we
characterized two novel
-defensin homologues in the rat. The rat may
be a useful model to investigate the function and contribution of
-defensins to host defense in the lung, kidney, and other tissues.
*
Corresponding author. Mailing address: Department of
Pediatrics, University of Iowa College of Medicine, Iowa City, IA
52242. Phone: (319) 356-4866. Fax: (319) 356-7171. E-mail:
paul-mccray{at}uiowa.edu.
Infection and Immunity, September 1999, p. 4827-4833, Vol. 67, No. 9
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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