MOUSE BETA-DEFENSIN-1 IS A FUNCTIONAL HOMOLOG OF HUMAN BETA-DEFENSIN-1

Defensin are 3-4 kDa antimicrobial peptides of which three distinct fa milies have been identified: alpha-defensin, beta-defensins, and insec t defensins. Recent investigations have shown that beta-defensins are present in the human airways and may be relevant to the pathogenesis o f cystic fibrosis (CF) lung disease. We report here the further charac terization of a recently identified mouse beta-defensin gene, Defb1, s ometimes referred to as mBD-1, which is homologous to the human airway beta defensin hBD-1. We report that Defb1 is expressed in a variety o f tissues including the airways and, similar to hBD-1, is not upregula ted by lipopolysaccharide (LPS). Defb1 was found to consist of two sma ll exons separated by a 16-kb intron and cytogenetic, and physical map ping linked it to the alpha defensin gene cluster on mouse Chromosome (Chr) 8. Functional studies demonstrate that, Like hBD-1, Defb1 demons trates a salt-sensitive antimicrobial activity against Pseudomonas aer uginosa. Of relevance to CF lung disease is the fact that neither the hBD-1 nor the mBD-1 peptides are active against Burkholderia cepacia.