Structure and Diversity of the Murine Cryptdin Gene Family

Cryptdins are antimicrobial peptides of the defensin family produced by mouse intestinal Paneth cells. Characterization of genomic and cDNA clones of cryptdins 1-3, 5, and 6 revealed that each of these genes has a two-exon structure. The prepro- and mature peptide coding regions are found on different exons separated by an intron of approximately 550 bp. The 5′ ends of cryptdin mRNAs are distinguished by a 45-nucleotide untranslated sequence (UTS) encoded completely by the first exon. This feature contrasts with the extended 5′ UTS of myeloid defensin mRNAs, which are coded by a third exon that appears to he unique to defensin genes expressed in hematopoietic cells. Sequencing of cryptdin cDNAs from both C3H/HeJ and 129/SVJ mouse small intestine demonstrated the presence of at least 16 different mRNAs, identifying cryptdins as the largest known defensin family. Amplification of these two-exon crypt defensin genes, followed by mutation-induced divergence at a limited number of positions, may have played an important role in the development of a broad-spectrum enteric defense system in the mouse.