Disease relevance of Defa1

• The most abundant enteric defensin, cryptdin-1, had antimicrobial activity against an attenuated phoP mutant of Salmonella typhimurium but was not active against the virulent wild-type parent [1].
• Gram-negative bacteria, Gram-positive bacteria, lipopolysaccharide, lipoteichoic acid, lipid A and muramyl dipeptide elicit cryptdin secretion [2].
• Recent work with short-circuit current measurements indicated that at least one cryptdin peptide, cryptdin 3, induces apical conductance(s) in Cl(-) secretory, including cystic fibrosis, epithelia [3].

Psychiatry related information on Defa1

• We also found changes in the circadian amplitude and/or phase of clock-controlled output systems, such as feeding behavior, body temperature, and enteric cryptdin expression [4].

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

• Cryptdin and CRS1C mRNAs are not detectable in adult mouse bone marrow, but probes specific for the 5'- or the 3'-untranslated regions of CRS4C mRNA hybridize to a moderately abundant 1.05-kilobase bone marrow mRNA in contrast to a highly abundant 0.75-kilobase mRNA in small intestine [7].
• Cryptdin is a defensin-related peptide, and its mRNA accumulates to high abundance in epithelial cells of intestinal crypts beginning in the second week of postnatal development [10].
• We speculate that the cryptdin/CRS genes evolved so that prepro regions encoded by exon 1 were conserved to allow the varied peptides coded by exon 2 to be directed into Paneth cell secretory granules [9].
• The cryptdin (Defcr) locus was assigned to mouse chromosome 8 by Southern blotting of DNAs from mouse/hamster somatic hybrid cell lines [10].
• Developmental regulation of cryptdin, a corticostatin/defensin precursor mRNA in mouse small intestinal crypt epithelium [11].

Associations of Defa1 with chemical compounds

• Cryptdin mRNA content in adult small intestine is independent both of T cell involvement and luminal bacteria [11].
• In situ hybridization of cryptdin cDNA to paraformaldehyde-fixed, frozen sections of adult jejunum and ileum showed intense and specific labeling of epithelial cells in the base of all crypts [11].

Other interactions of Defa1

• The mouse cryptdin-4 gene is expressed with positional specificity along the longitudinal intestinal axis, and cryptdin genes are active in the intestinal epithelium prior to Paneth cell differentiation [12].

Analytical, diagnostic and therapeutic context of Defa1

• In contrast, intestinal content of cryptdin-1 and -5 mRNAs was equivalent in duodenum, jejunum, and ileum, and Northern blot hybridization experiments were consistent with both sets of data [13].
• Several cryptdin peptides have been purified from rinses of adult mouse small intestine by gel filtration and reverse-phase high performance liquid chromatography [14].
• In the present study, we characterized the cryptdin 3-induced anion channel activity in human embryonic kidney (HEK) cells with single-channel patch-clamp techniques [3].
• In situ hybridization analysis showed that the mRNA of cryptdin was expressed in the suprabasal keratinocytes of the skin in embryonic and neonatal days and then shifted to the hair bulbs in the skin of adult mice [15].
• In this study, we detected the expression of mRNA for the defensin cryptdin in BALB/c mouse skin by means of reverse transcriptase PCR amplification [15].

References