Skip to main content
Molecular Medicine logoLink to Molecular Medicine
. 1997 Jun;3(6):403–411.

Cystic fibrosis of the pancreas: involvement of MUC6 mucin in obstruction of pancreatic ducts.

C J Reid 1, K Hyde 1, S B Ho 1, A Harris 1
PMCID: PMC2230211  PMID: 9234245

Abstract

BACKGROUND: Cystic fibrosis (CF) is characterized by pancreatic destruction following the gradual obstruction of small pancreatic ducts, from the mid-trimester of gestation onwards. To date, the material causing the obstruction has not been identified. The MUC6 mucin cDNA was isolated from human stomach and has been shown to be expressed in a number of other tissues in the gastrointestinal tract, including the gall bladder and parts of the ileum and colon. MATERIALS AND METHODS: We have examined the expression of MUC6 mucin in the human pancreas, both during development and postnatally, by mRNA in situ hybridization and immunocytochemistry. RESULTS: In this report we establish that MUC6 transcripts are abundant in pancreatic epithelial cells and show a very similar pattern of expression in the epithelium lining small ducts and centroacinar cells to that shown by the cystic fibrosis transmembrane conductance regulator gene (CFTR). In addition, material obstructing the pancreatic ducts of CF pancreas was shown to contain MUC6 mucin. CONCLUSION: We have identified MUC6 mucin as a significant constituent of the material obstructing the small pancreatic ducts in CF.

Full text

PDF
403

Images in this article

Selected References

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

  1. Anderson M. P., Rich D. P., Gregory R. J., Smith A. E., Welsh M. J. Generation of cAMP-activated chloride currents by expression of CFTR. Science. 1991 Feb 8;251(4994):679–682. doi: 10.1126/science.1704151. [DOI] [PubMed] [Google Scholar]
  2. Aubert J. P., Porchet N., Crepin M., Duterque-Coquillaud M., Vergnes G., Mazzuca M., Debuire B., Petitprez D., Degand P. Evidence for different human tracheobronchial mucin peptides deduced from nucleotide cDNA sequences. Am J Respir Cell Mol Biol. 1991 Aug;5(2):178–185. doi: 10.1165/ajrcmb/5.2.178. [DOI] [PubMed] [Google Scholar]
  3. Balagué C., Audié J. P., Porchet N., Real F. X. In situ hybridization shows distinct patterns of mucin gene expression in normal, benign, and malignant pancreas tissues. Gastroenterology. 1995 Sep;109(3):953–964. doi: 10.1016/0016-5085(95)90406-9. [DOI] [PubMed] [Google Scholar]
  4. Batra S. K., Metzgar R. S., Hollingsworth M. A. Human Muc 1 mucin gene expression in the fetal pancreas. Pancreas. 1992;7(3):391–393. doi: 10.1097/00006676-199205000-00018. [DOI] [PubMed] [Google Scholar]
  5. Boué A., Muller F., Nezelof C., Oury J. F., Duchatel F., Dumez Y., Aubry M. C., Boué J. Prenatal diagnosis in 200 pregnancies with a 1-in-4 risk of cystic fibrosis. Hum Genet. 1986 Nov;74(3):288–297. doi: 10.1007/BF00282551. [DOI] [PubMed] [Google Scholar]
  6. Chambers J. A., Hollingsworth M. A., Trezise A. E., Harris A. Developmental expression of mucin genes MUC1 and MUC2. J Cell Sci. 1994 Feb;107(Pt 2):413–424. doi: 10.1242/jcs.107.2.413. [DOI] [PubMed] [Google Scholar]
  7. Crawford I., Maloney P. C., Zeitlin P. L., Guggino W. B., Hyde S. C., Turley H., Gatter K. C., Harris A., Higgins C. F. Immunocytochemical localization of the cystic fibrosis gene product CFTR. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9262–9266. doi: 10.1073/pnas.88.20.9262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. De Bolós C., Garrido M., Real F. X. MUC6 apomucin shows a distinct normal tissue distribution that correlates with Lewis antigen expression in the human stomach. Gastroenterology. 1995 Sep;109(3):723–734. doi: 10.1016/0016-5085(95)90379-8. [DOI] [PubMed] [Google Scholar]
  9. Gray M. A., Greenwell J. R., Argent B. E. Secretin-regulated chloride channel on the apical plasma membrane of pancreatic duct cells. J Membr Biol. 1988 Oct;105(2):131–142. doi: 10.1007/BF02009166. [DOI] [PubMed] [Google Scholar]
  10. Gum J. R., Hicks J. W., Swallow D. M., Lagace R. L., Byrd J. C., Lamport D. T., Siddiki B., Kim Y. S. Molecular cloning of cDNAs derived from a novel human intestinal mucin gene. Biochem Biophys Res Commun. 1990 Aug 31;171(1):407–415. doi: 10.1016/0006-291x(90)91408-k. [DOI] [PubMed] [Google Scholar]
  11. Gum J. R., Jr, Hicks J. W., Toribara N. W., Rothe E. M., Lagace R. E., Kim Y. S. The human MUC2 intestinal mucin has cysteine-rich subdomains located both upstream and downstream of its central repetitive region. J Biol Chem. 1992 Oct 25;267(30):21375–21383. [PubMed] [Google Scholar]
  12. Harris A., Chalkley G., Goodman S., Coleman L. Expression of the cystic fibrosis gene in human development. Development. 1991 Sep;113(1):305–310. doi: 10.1242/dev.113.1.305. [DOI] [PubMed] [Google Scholar]
  13. Ho S. B., Roberton A. M., Shekels L. L., Lyftogt C. T., Niehans G. A., Toribara N. W. Expression cloning of gastric mucin complementary DNA and localization of mucin gene expression. Gastroenterology. 1995 Sep;109(3):735–747. doi: 10.1016/0016-5085(95)90380-1. [DOI] [PubMed] [Google Scholar]
  14. Kopelman H., Durie P., Gaskin K., Weizman Z., Forstner G. Pancreatic fluid secretion and protein hyperconcentration in cystic fibrosis. N Engl J Med. 1985 Feb 7;312(6):329–334. doi: 10.1056/NEJM198502073120601. [DOI] [PubMed] [Google Scholar]
  15. Lan M. S., Batra S. K., Qi W. N., Metzgar R. S., Hollingsworth M. A. Cloning and sequencing of a human pancreatic tumor mucin cDNA. J Biol Chem. 1990 Sep 5;265(25):15294–15299. [PubMed] [Google Scholar]
  16. Riordan J. R., Rommens J. M., Kerem B., Alon N., Rozmahel R., Grzelczak Z., Zielenski J., Lok S., Plavsic N., Chou J. L. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science. 1989 Sep 8;245(4922):1066–1073. doi: 10.1126/science.2475911. [DOI] [PubMed] [Google Scholar]
  17. Toribara N. W., Roberton A. M., Ho S. B., Kuo W. L., Gum E., Hicks J. W., Gum J. R., Jr, Byrd J. C., Siddiki B., Kim Y. S. Human gastric mucin. Identification of a unique species by expression cloning. J Biol Chem. 1993 Mar 15;268(8):5879–5885. [PubMed] [Google Scholar]
  18. Trezise A. E., Chambers J. A., Wardle C. J., Gould S., Harris A. Expression of the cystic fibrosis gene in human foetal tissues. Hum Mol Genet. 1993 Mar;2(3):213–218. doi: 10.1093/hmg/2.3.213. [DOI] [PubMed] [Google Scholar]

Articles from Molecular Medicine are provided here courtesy of The Feinstein Institute for Medical Research at North Shore LIJ

RESOURCES