Mice lacking transforming growth factor alpha have an increased susceptibility to dextran sulfate-induced colitis

Gastroenterology. 1997 Sep;113(3):825-32. doi: 10.1016/s0016-5085(97)70177-x.


Background & aims: There is indirect evidence that transforming growth factor alpha (TGF-alpha) is an important mediator of mucosal defense and repair. TGF-alpha knockout mice and TGF-alpha-deficient mice (wa-1) provide novel approaches to evaluate the role of TGF-alpha in preserving the integrity of the colon.

Methods: Colitis was induced by oral administration of dextran sodium sulfate (DSS, 5 g/dL) to knockout mice, their genetic controls (GC), wa-1 mice, and BALB/c mice. TGF-alpha was also administered intraperitoneally to wa-1 mice to evaluate the effect of exogenous TGF-alpha in DSS colitis.

Results: In response to DSS, nearly 60% of the entire colonic mucosa was destroyed in knockout and wa-1 mice, compared with 22% in GC mice and 16% in BALB/ c mice. Body weight loss was doubled in knockout (28%) and wa-1 mice (23%) compared with GC (11%) and Balb/c mice (12%). TGF-alpha application to wa-1 mice reduced the severity of mucosal injury by almost 70% compared with controls.

Conclusions: The marked susceptibility of TGF-alpha knockout and wa-1 mice to DSS and the obvious amelioration of the colonic injury by exogenous TGF-alpha application in wa-1 mice suggest that TGF-alpha is a mediator of protection and/or healing mechanisms in the colon.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colitis / chemically induced*
  • Colitis / genetics*
  • Colitis / pathology
  • Colon / pathology
  • Dextran Sulfate*
  • Drinking
  • Female
  • Genetic Predisposition to Disease
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout / genetics*
  • Mice, Mutant Strains
  • Reference Values
  • Solutions
  • Transforming Growth Factor alpha / deficiency
  • Transforming Growth Factor alpha / genetics*
  • Transforming Growth Factor alpha / pharmacology


  • Solutions
  • Transforming Growth Factor alpha
  • Dextran Sulfate