Paneth cells are epithelial granulocytes at the base of the crypts of Lieberkühn in the small intestine of many mammalian species. These secretory cells contribute to mucosal barrier function by the apical release of granules containing a variety of antimicrobial products, including peptides termed cryptdins, for crypt defensins. In mice, six Paneth cell defensins have been characterized at the peptide level that have potent antimicrobial activities equivalent to or greater than that of rabbit neutrophil defensin NP-1. Cryptdin peptides that differ only by single amino acid substitutions have been shown to exhibit a high degree of specificity against certain target microorganisms. Cryptdins are coded by separate, two-exon genes that are located on chromosome 8 in both mice and humans. Human Paneth cells contain high levels of two different defensin mRNAs, but in mice at least 19 cryptdin isoforms are predicted from cDNA sequencing data. The mouse cryptdin-4 gene is expressed with positional specificity al...