A paradoxical reduction in susceptibility to colonic injury upon targeted transgenic ablation of goblet cells

Hiroshi Itoh, Paul L. Beck, Nagamu Inoue, Ramnik Xavier, Daniel K. Podolsky

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Goblet cells are the major mucus-producing cells of the intestine and are presumed to play an important role in mucosal protection. However, their functional role has not been directly assessed in vivo. In initial studies, a 5' flanking sequence of the murine intestinal trefoil factor (ITF) gene was found to confer goblet cell-specific expression of a transgene. To assess the role of goblet cells in the intestine, we generated transgenic mice in which ~60% of goblet cells were ablated by the expression of an attenuated diphtheria toxin [DT) gene driven by the ITF promoter; other cell lineages were unaffected. We administered 2 exogenous agents, dextran sodium sulfate (DSS) and acetic acid, to assess the susceptibility of mITF/DT-A transgenic mice to colonic injury. After oral administration of DSS, 55% of control mice died, whereas DT transgenic mice retained their body weight and less than 5% died. Similarly, 30% of the wild-type mice died after mucosal administration of acetic acid, compared with 3.2% of the transgenic mice. Despite the reduction goblet-cell number, the total amount of ITF was increased in the mITF/DT-A transgenic mice, indicating inducible-compensatory mechanisms. These results suggest that goblet cells contribute to mucosal protection and repair predominantly through production of trefoil peptides.

Original languageEnglish
Pages (from-to)1539-1547
Number of pages9
JournalJournal of Clinical Investigation
Volume104
Issue number11
Publication statusPublished - 1999 Dec
Externally publishedYes

Fingerprint

Goblet Cells
Diphtheria Toxin
Transgenic Mice
Wounds and Injuries
Dextran Sulfate
Acetic Acid
Intestines
Mucosal Administration
5' Flanking Region
Cell Lineage
Mucus
Transgenes
Genes
Oral Administration
Cell Count
Body Weight
Trefoil Factor-3

ASJC Scopus subject areas

  • Medicine(all)

Cite this

A paradoxical reduction in susceptibility to colonic injury upon targeted transgenic ablation of goblet cells. / Itoh, Hiroshi; Beck, Paul L.; Inoue, Nagamu; Xavier, Ramnik; Podolsky, Daniel K.

In: Journal of Clinical Investigation, Vol. 104, No. 11, 12.1999, p. 1539-1547.

Research output: Contribution to journalArticle

Itoh, Hiroshi ; Beck, Paul L. ; Inoue, Nagamu ; Xavier, Ramnik ; Podolsky, Daniel K. / A paradoxical reduction in susceptibility to colonic injury upon targeted transgenic ablation of goblet cells. In: Journal of Clinical Investigation. 1999 ; Vol. 104, No. 11. pp. 1539-1547.
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