Skip to main content
PMC home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1989 May 1;108(5):1687–1695. doi: 10.1083/jcb.108.5.1687

Developmental regulation of cryptdin, a corticostatin/defensin precursor mRNA in mouse small intestinal crypt epithelium

PMCID: PMC2115551  PMID: 2715173

Abstract

Cryptdin mRNA codes for the apparent precursor to a corticostatin/defensin-related peptide that accumulates to high levels in mouse intestinal crypt epithelium during postnatal development. The primary structure, intestinal cell distribution, and developmental appearance of cryptdin mRNA have been determined. Cryptdin mRNA is 450- 480 nucleotides long. Translation of the partial cryptdin cDNA sequence reveals a 70-amino acid open reading frame that includes 32 carboxy- terminal residues that align with those in the consensus sequence, C.CR...C....ER..G.C....CCR, which is a common feature of leukocyte defensins and lung corticostatins (Selsted, M. E., D. M. Brown, R. J. DeLange, S. S. L. Harwig, and R. I. Lehrer. 1985. J. Biol. Chem. 260:4579-4584; Zhu, Q., J. Hu, S. Mulay, F. Esch, S. Shimasaki, and S. Solomon. 1988. Proc. Natl. Acad. Sci. USA. 85:592-596). 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. Analysis of sections from suckling mice showed that cryptdin mRNA is detectable in 10-20% of crypts in 10-d-old mice, in approximately 80% of crypts in 16- d-old mice, and in all crypts of mice 20 d and older. During the fourth week, the sequence accumulates in crypts to the maximal adult level. Cryptdin mRNA content in adult small intestine is independent both of T cell involvement and luminal bacteria. The role of cryptdin in small bowel physiology remains to be determined: cryptdin may inhibit bacterial translocation, modulate intestinal hormone synthesis, influence hormonal sensitivity of the intestinal epithelium, or exhibit a multiplicity of related activities.

Full Text

The Full Text of this article is available as a PDF (3.1 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Altmann G. G., Enesco M. Cell number as a measure of distribution and renewal of epithelial cells in the small intestine of growing and adult rats. Am J Anat. 1967 Sep;121(2):319–336. doi: 10.1002/aja.1001210210. [DOI] [PubMed] [Google Scholar]
  2. Angerer L. M., Cox K. H., Angerer R. C. Demonstration of tissue-specific gene expression by in situ hybridization. Methods Enzymol. 1987;152:649–661. doi: 10.1016/0076-6879(87)52071-7. [DOI] [PubMed] [Google Scholar]
  3. Bach A. C., 2nd, Selsted M. E., Pardi A. Two-dimensional NMR studies of the antimicrobial peptide NP-5. Biochemistry. 1987 Jul 14;26(14):4389–4397. doi: 10.1021/bi00388a030. [DOI] [PubMed] [Google Scholar]
  4. Biggin M. D., Gibson T. J., Hong G. F. Buffer gradient gels and 35S label as an aid to rapid DNA sequence determination. Proc Natl Acad Sci U S A. 1983 Jul;80(13):3963–3965. doi: 10.1073/pnas.80.13.3963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Birkenmeier E. H., Gordon J. I. Developmental regulation of a gene that encodes a cysteine-rich intestinal protein and maps near the murine immunoglobulin heavy chain locus. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2516–2520. doi: 10.1073/pnas.83.8.2516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  7. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Elmes M. E., Stanton M. R., Howells C. H., Lowe G. H. Relation between the mucosal flora and Paneth cell population of human jejunum and ileum. J Clin Pathol. 1984 Nov;37(11):1268–1271. doi: 10.1136/jcp.37.11.1268. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Erlandsen S. L., Chase D. G. Paneth cell function: phagocytosis and intracellular digestion of intestinal microorganisms. I. Hexamita muris. J Ultrastruct Res. 1972 Nov;41(3):296–318. doi: 10.1016/s0022-5320(72)90071-8. [DOI] [PubMed] [Google Scholar]
  10. Erlandsen S. L., Parsons J. A., Taylor T. D. Ultrastructural immunocytochemical localization of lysozyme in the Paneth cells of man. J Histochem Cytochem. 1974 Jun;22(6):401–413. doi: 10.1177/22.6.401. [DOI] [PubMed] [Google Scholar]
  11. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  12. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  13. Ganz T., Selsted M. E., Szklarek D., Harwig S. S., Daher K., Bainton D. F., Lehrer R. I. Defensins. Natural peptide antibiotics of human neutrophils. J Clin Invest. 1985 Oct;76(4):1427–1435. doi: 10.1172/JCI112120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ganz T., Sherman M. P., Selsted M. E., Lehrer R. I. Newborn rabbit alveolar macrophages are deficient in two microbicidal cationic peptides, MCP-1 and MCP-2. Am Rev Respir Dis. 1985 Oct;132(4):901–904. doi: 10.1164/arrd.1985.132.4.901. [DOI] [PubMed] [Google Scholar]
  15. George D. G., Barker W. C., Hunt L. T. The protein identification resource (PIR). Nucleic Acids Res. 1986 Jan 10;14(1):11–15. doi: 10.1093/nar/14.1.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Guy-Grand D., Griscelli C., Vassalli P. The mouse gut T lymphocyte, a novel type of T cell. Nature, origin, and traffic in mice in normal and graft-versus-host conditions. J Exp Med. 1978 Dec 1;148(6):1661–1677. doi: 10.1084/jem.148.6.1661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hammer M. F., Schilling J. W., Prager E. M., Wilson A. C. Recruitment of lysozyme as a major enzyme in the mouse gut: duplication, divergence, and regulatory evolution. J Mol Evol. 1987;24(3):272–279. doi: 10.1007/BF02111240. [DOI] [PubMed] [Google Scholar]
  18. Henning S. J. Ontogeny of enzymes in the small intestine. Annu Rev Physiol. 1985;47:231–245. doi: 10.1146/annurev.ph.47.030185.001311. [DOI] [PubMed] [Google Scholar]
  19. Herbst J. J., Sunshine P. Postnatal development of the small intestine of the rat. Changes in mucosal morphology at weaning. Pediatr Res. 1969 Jan;3(1):27–33. doi: 10.1203/00006450-196901000-00004. [DOI] [PubMed] [Google Scholar]
  20. Huang W. M., Gibson S. J., Facer P., Gu J., Polak J. M. Improved section adhesion for immunocytochemistry using high molecular weight polymers of L-lysine as a slide coating. Histochemistry. 1983;77(2):275–279. doi: 10.1007/BF00506570. [DOI] [PubMed] [Google Scholar]
  21. Klein R. M., McKenzie J. C. The role of cell renewal in the ontogeny of the intestine. II. Regulation of cell proliferation in adult, fetal, and neonatal intestine. J Pediatr Gastroenterol Nutr. 1983 May;2(2):204–228. [PubMed] [Google Scholar]
  22. Koldovsky O., Sunshine P., Kretchmer N. Cellular migration of intestinal epithelia in suckling and weaned rats. Nature. 1966 Dec 17;212(5068):1389–1390. doi: 10.1038/2121389a0. [DOI] [PubMed] [Google Scholar]
  23. Lehrer R. I., Selsted M. E., Szklarek D., Fleischmann J. Antibacterial activity of microbicidal cationic proteins 1 and 2, natural peptide antibiotics of rabbit lung macrophages. Infect Immun. 1983 Oct;42(1):10–14. doi: 10.1128/iai.42.1.10-14.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. MOOG F. Developmental adaptations of alkaline phosphatases in the small intestine. Fed Proc. 1962 Jan-Feb;21:51–56. [PubMed] [Google Scholar]
  25. Marasco W. A., Phan S. H., Krutzsch H., Showell H. J., Feltner D. E., Nairn R., Becker E. L., Ward P. A. Purification and identification of formyl-methionyl-leucyl-phenylalanine as the major peptide neutrophil chemotactic factor produced by Escherichia coli. J Biol Chem. 1984 May 10;259(9):5430–5439. [PubMed] [Google Scholar]
  26. Ouellette A. J., Cordell B. Accumulation of abundant messenger ribonucleic acids during postnatal development of mouse small intestine. Gastroenterology. 1988 Jan;94(1):114–121. doi: 10.1016/0016-5085(88)90618-x. [DOI] [PubMed] [Google Scholar]
  27. Perry R. P., La Torre J., Kelley D. E., Greenberg J. R. On the lability of poly(A) sequences during extraction of messenger RNA from polyribosomes. Biochim Biophys Acta. 1972 Mar 14;262(2):220–226. doi: 10.1016/0005-2787(72)90236-5. [DOI] [PubMed] [Google Scholar]
  28. Raul F., Simon P., Kedinger M., Haffen K. Intestinal enzymes activities in isolated villus and crypt cells during postnatal development of the rat. Cell Tissue Res. 1977 Jan 12;176(2):167–178. doi: 10.1007/BF00229460. [DOI] [PubMed] [Google Scholar]
  29. Rave N., Crkvenjakov R., Boedtker H. Identification of procollagen mRNAs transferred to diazobenzyloxymethyl paper from formaldehyde agarose gels. Nucleic Acids Res. 1979 Aug 10;6(11):3559–3567. doi: 10.1093/nar/6.11.3559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  31. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Satoh Y., Ishikawa K., Ono K., Vollrath L. Quantitative light microscopic observations on Paneth cells of germ-free and ex-germ-free Wistar rats. Digestion. 1986;34(2):115–121. doi: 10.1159/000199319. [DOI] [PubMed] [Google Scholar]
  33. Satoh Y., Vollrath L. Quantitative electron microscopic observations on Paneth cells of germfree and ex-germfree Wistar rats. Anat Embryol (Berl) 1986;173(3):317–322. doi: 10.1007/BF00318915. [DOI] [PubMed] [Google Scholar]
  34. Selsted M. E., Brown D. M., DeLange R. J., Harwig S. S., Lehrer R. I. Primary structures of six antimicrobial peptides of rabbit peritoneal neutrophils. J Biol Chem. 1985 Apr 25;260(8):4579–4584. [PubMed] [Google Scholar]
  35. Selsted M. E., Brown D. M., DeLange R. J., Lehrer R. I. Primary structures of MCP-1 and MCP-2, natural peptide antibiotics of rabbit lung macrophages. J Biol Chem. 1983 Dec 10;258(23):14485–14489. [PubMed] [Google Scholar]
  36. Selsted M. E., Harwig S. S., Ganz T., Schilling J. W., Lehrer R. I. Primary structures of three human neutrophil defensins. J Clin Invest. 1985 Oct;76(4):1436–1439. doi: 10.1172/JCI112121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Selsted M. E., Harwig S. S. Purification, primary structure, and antimicrobial activities of a guinea pig neutrophil defensin. Infect Immun. 1987 Sep;55(9):2281–2286. doi: 10.1128/iai.55.9.2281-2286.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Selsted M. E., Szklarek D., Lehrer R. I. Purification and antibacterial activity of antimicrobial peptides of rabbit granulocytes. Infect Immun. 1984 Jul;45(1):150–154. doi: 10.1128/iai.45.1.150-154.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Staden R. Computer methods to aid the determination and analysis of DNA sequences. Biochem Soc Trans. 1984 Dec;12(6):1005–1008. doi: 10.1042/bst0121005. [DOI] [PubMed] [Google Scholar]
  40. Staden R. The current status and portability of our sequence handling software. Nucleic Acids Res. 1986 Jan 10;14(1):217–231. doi: 10.1093/nar/14.1.217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Stanfield R. L., Westbrook E. M., Selsted M. E. Characterization of two crystal forms of human defensin neutrophil cationic peptide 1, a naturally occurring antimicrobial peptide of leukocytes. J Biol Chem. 1988 Apr 25;263(12):5933–5935. [PubMed] [Google Scholar]
  42. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Westbrook E. M., Lehrer R. I., Selsted M. E. Characterization of two crystal forms of neutrophil cationic protein NP2, a naturally occurring broad-spectrum antimicrobial agent from leukocytes. J Mol Biol. 1984 Sep 25;178(3):783–785. doi: 10.1016/0022-2836(84)90252-3. [DOI] [PubMed] [Google Scholar]
  44. Zhu Q. Z., Hu J., Mulay S., Esch F., Shimasaki S., Solomon S. Isolation and structure of corticostatin peptides from rabbit fetal and adult lung. Proc Natl Acad Sci U S A. 1988 Jan;85(2):592–596. doi: 10.1073/pnas.85.2.592. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES