Peptide localization and gene structure of cryptdin 4, a differentially expressed mouse paneth cell alpha-defensin

Infect Immun. 1999 Dec;67(12):6643-51. doi: 10.1128/IAI.67.12.6643-6651.1999.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Immunohistochemistry
  • Intestine, Small / metabolism
  • Mice
  • Molecular Sequence Data
  • Paneth Cells / metabolism*
  • Protein Precursors / chemistry
  • Protein Precursors / genetics*
  • Protein Precursors / metabolism*
  • Sequence Analysis, DNA

Substances

  • Protein Precursors
  • cryptdin

Associated data

  • GENBANK/AF178040
  • GENBANK/AF178041
  • GENBANK/AF178042
  • GENBANK/AF178043
  • GENBANK/AF178044