Molecular cloning and characterization of rat genes encoding homologues of human beta-defensins.
beta-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 beta-defensins have been identified. Here, we report the identification of two genes encoding beta-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 beta-defensin-1 (HBD-1) gene and mouse beta-defensin-1 gene at both the nucleic acid and amino acid levels and was termed rat beta-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 beta-defensins. The beta-defensin genes mapped closely on rat chromosome 16 and were closely linked to the alpha-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 approximately 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 beta-defensin homologues in the rat. The rat may be a useful model to investigate the function and contribution of beta-defensins to host defense in the lung, kidney, and other tissues.
Jia
H P
HP
Department of Pediatrics, University of Iowa College of Medicine, Iowa City, Iowa, USA.
Mills
J N
JN
Barahmand-Pour
F
F
Nishimura
D
D
Mallampali
R K
RK
Wang
G
G
Wiles
K
K
Tack
B F
BF
Bevins
C L
CL
McCray
P B
PB
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D001992:Bronchoalveolar Lavage Fluid; D002417:Cattle; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D018076:DNA, Complementary; D023082:Defensins; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley; D017386:Sequence Homology, Amino Acid; D012965:Sodium Chloride; D014018:Tissue Distribution; D023083:beta-Defensins
C406407:DEFB1 protein, human; D018076:DNA, Complementary; D023082:Defensins; D011506:Proteins; D012333:RNA, Messenger; D023083:beta-Defensins; D012965:Sodium Chloride