First Author | Ouellette AJ | Year | 1999 |
Journal | Infect Immun | Volume | 67 |
Issue | 12 | Pages | 6643-51 |
PubMed ID | 10569786 | Mgi Jnum | J:58542 |
Mgi Id | MGI:1347772 | Doi | 10.1128/iai.67.12.6643-6651.1999 |
Citation | Ouellette AJ, et al. (1999) Peptide localization and gene structure of cryptdin 4, a differentially expressed mouse paneth cell alpha-defensin. Infect Immun 67(12):6643-51 |
abstractText | Paneth cells in crypts of the small intestine express antimicrobial peptides, including alpha-defensins, termed cryptdins in mice. Of the known Paneth cell alpha-defensins, the cryptdin 4 gene is unique, because it is inactive in the duodenum and expressed at maximal levels in the distal small bowel (D. Darmoul and A. J. Ouellette, Am. J. Physiol. 271:G68-G74, 1996). With a cryptdin 4-specific antibody, immunohistochemical staining of ileal Paneth cells was strong and specific for cytoplasmic granules, demonstrating that this microbicidal peptide is a secretory product of Paneth cells in the distal small intestine. Consistent with the pattern of cryptdin 4 mRNA distribution along the length of the gut, the cryptdin 4 peptide was not detected in duodenum. Structurally, the cryptdin 4 gene resembles other Paneth cell alpha-defensin genes. Its two exons, transcriptional start site, intron, splice sites, and 3' flanking sequences are characteristic of the highly conserved mouse alpha-defensin genes. However, in the region upstream of the transcriptional initiation site, the cryptdin 4 gene contains a repeated 130-bp element that is unique to this alpha-defensin gene. Every independent cryptdin 4 genomic clone examined carries the repeated element, which contains putative recognition sequences for TF-IID-EIIA, cMyc-RS-1, and IgHC.2/CuE1.1; the repeat proximal to the start of transcription replaces DNA at the corresponding position in other mouse alpha-defensin genes. We speculate that this unique duplicated element may have a cis-acting regulatory role in the positional specificity of cryptdin 4 gene expression. |