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Gene Review

Defa1  -  defensin, alpha 1

Mus musculus

Synonyms: Alpha-defensin 1, Cryptdin-1, Defcr, Defcr1, Defensin-related cryptdin peptide, ...
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Disease relevance of Defa1


Psychiatry related information on Defa1


High impact information on Defa1

  • In mouse small intestine, matrilysin colocalized with alpha-defensins (cryptdins) in Paneth cell granules, and in vitro it cleaved the pro segment from cryptdin precursors [5].
  • The peptides are coded by individual, two-exon genes that map to homologous regions of chromosome 8 in mice and humans, and the differential expression of certain mouse cryptdin genes provides markers for studies of crypt ontogeny and epithelial cell differentiation and lineage determination [6].
  • The presence of several enteric defensins in the intestinal epithelium, evidence of their presence in the lumen, and the antibacterial activity of cryptdin-1 suggest that these peptides contribute to the antimicrobial barrier function of the small bowel mucosa [1].
  • Biochemical and immunologic analysis of the luminal contents of the small intestine suggest that cryptdin peptides are secreted into the lumen, similar to Paneth cell secretion of lysozyme [1].
  • Immunohistochemical localization demonstrated that cryptdin-1, and probably cryptdins 2 and 3, occur exclusively in Paneth cells, where the peptides appear to be associated with cytoplasmic granules [1].

Biological context of Defa1

  • Nucleotide sequences corresponding to the deduced prepro-coding regions of cryptdin, CRS1C, and CRS4C mRNAs contain a highly conserved 200-base pair region of 92% sequence similarity (CSE.2), but the mRNAs are not homologous otherwise [7].
  • To help define the intestinal role of cryptdin, cryptdin-related sequence (CRS) mRNAs have been characterized with respect to developmental regulation, sequence homology, putative coding function, and occurrence in myeloid cells [7].
  • Thus, both the Defcr-rs1 and the Defcr genes are expressed in Paneth cells and both are genetically inseparable within 1.58 cM on Chromosome 8 [8].
  • Analysis of introns suggests that the ancestral cryptdin and CRS4C genes may have diverged from a common ancestor in the distant past and expanded only recently [9].
  • The CRS4C genes closely resemble cryptdin genes, having a two-exon structure with highly conserved transcription start sites, intron-exon junctions, and a single intron of approximately 550 bp [9].

Anatomical context of Defa1


Associations of Defa1 with chemical compounds


Other interactions of Defa1


Analytical, diagnostic and therapeutic context of Defa1


  1. Enteric defensins: antibiotic peptide components of intestinal host defense. Selsted, M.E., Miller, S.I., Henschen, A.H., Ouellette, A.J. J. Cell Biol. (1992) [Pubmed]
  2. Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response to bacteria. Ayabe, T., Satchell, D.P., Wilson, C.L., Parks, W.C., Selsted, M.E., Ouellette, A.J. Nat. Immunol. (2000) [Pubmed]
  3. Cryptdin 3 forms anion selective channels in cytoplasmic membranes of human embryonic kidney cells. Yue, G., Merlin, D., Selsted, M.E., Lencer, W.I., Madara, J.L., Eaton, D.C. Am. J. Physiol. Gastrointest. Liver Physiol. (2002) [Pubmed]
  4. Long-lived {alpha}MUPA transgenic mice exhibit pronounced circadian rhythms. Froy, O., Chapnik, N., Miskin, R. Am. J. Physiol. Endocrinol. Metab. (2006) [Pubmed]
  5. Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense. Wilson, C.L., Ouellette, A.J., Satchell, D.P., Ayabe, T., López-Boado, Y.S., Stratman, J.L., Hultgren, S.J., Matrisian, L.M., Parks, W.C. Science (1999) [Pubmed]
  6. Paneth cells and innate immunity in the crypt microenvironment. Ouellette, A.J. Gastroenterology (1997) [Pubmed]
  7. A novel mouse gene family coding for cationic, cysteine-rich peptides. Regulation in small intestine and cells of myeloid origin. Ouellette, A.J., Lualdi, J.C. J. Biol. Chem. (1990) [Pubmed]
  8. The defensin-related murine CRS1C gene: expression in Paneth cells and linkage to Defcr, the cryptdin locus. Lin, M.Y., Munshi, I.A., Ouellette, A.J. Genomics (1992) [Pubmed]
  9. A family of defensin-like genes codes for diverse cysteine-rich peptides in mouse Paneth cells. Huttner, K.M., Ouellette, A.J. Genomics (1994) [Pubmed]
  10. Localization of the cryptdin locus on mouse chromosome 8. Ouellette, A.J., Pravtcheva, D., Ruddle, F.H., James, M. Genomics (1989) [Pubmed]
  11. Developmental regulation of cryptdin, a corticostatin/defensin precursor mRNA in mouse small intestinal crypt epithelium. Ouellette, A.J., Greco, R.M., James, M., Frederick, D., Naftilan, J., Fallon, J.T. J. Cell Biol. (1989) [Pubmed]
  12. Paneth cell defensins: endogenous peptide components of intestinal host defense. Ouellette, A.J., Selsted, M.E. FASEB J. (1996) [Pubmed]
  13. Positional specificity of defensin gene expression reveals Paneth cell heterogeneity in mouse small intestine. Darmoul, D., Ouellette, A.J. Am. J. Physiol. (1996) [Pubmed]
  14. Characterization of luminal paneth cell alpha-defensins in mouse small intestine. Attenuated antimicrobial activities of peptides with truncated amino termini. Ouellette, A.J., Satchell, D.P., Hsieh, M.M., Hagen, S.J., Selsted, M.E. J. Biol. Chem. (2000) [Pubmed]
  15. Detection of cryptdin in mouse skin. Shirafuji, Y., Oono, T., Kanzaki, H., Hirakawa, S., Arata, J. Clin. Diagn. Lab. Immunol. (1999) [Pubmed]
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