POSITIONAL SPECIFICITY OF DEFENSIN GENE-EXPRESSION REVEALS PANETH CELL HETEROGENEITY IN MOUSE SMALL-INTESTINE

Cryptdins are antimicrobial peptides of the defensin family that are e xpressed specifically by Paneth cells in small intestinal crypts (M. E . Selsted, S. I. Miller, A. H. Henschen, and A. J. Ouellette. J. Cell Biol. 118: 929-936, 1992), and at least 17 cryptdin isoforms have been reported in mouse small intestine (A. J. Ouellette, M. M. Hsieh, M. T . Nosek, D. F. Cano-Gauci, K. M. Huttner, R. N. Buick, and M. E. Selst ed. Infect. Immun. 62: 5040-5047, 1994). Analysis of cryptdin gene exp ression in adult mouse small bowel revealed that the cryptdin-4 isofor m is differentially expressed along the proximal-to-distal intestinal axis. By peptide-specific reverse transcriptase-polymerase chain react ion-based assays, cryptdin-4 mRNA was found to be absent from the prox imal small bowel, increasing to maximal levels in the ileum. In contra st, intestinal content of cryptdin-1 and -5 mRNAs was equivalent in du odenum, jejunum, and ileum, and Northern blot hybridization experiment s were consistent with both sets of data. Similarly, individual crypts isolated fi om duodenum contain cryptdin-1 mRNA but not cryptdin-4 mR NA. Taken together, the results show that Paneth cells are heterogeneo us, depending on their position along the longitudinal axis of the sma ll bowel. The positional. specificity of defensin gene expression sugg ests that cryptdins may be useful markers for investigating the establ ishment and maintenance of this epithelial lineage in the mouse small intestine.