title: Mice lacking transforming growth factor alpha have an increased susceptibility to dextran sulfate-induced colitis.
abstract: OBJECTIVE
  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.
authors.affiliation: Inflammatory Bowel Disease Center, Harbor-UCLA Medical Center, Torrance, USA.
authors.forename: B
authors.initials: B
authors.lastname: Egger
authors.forename: F
authors.initials: F
authors.lastname: Procaccino
authors.forename: J
authors.initials: J
authors.lastname: Lakshmanan
authors.forename: M
authors.initials: M
authors.lastname: Reinshagen
authors.forename: P
authors.initials: P
authors.lastname: Hoffmann
authors.forename: A
authors.initials: A
authors.lastname: Patel
authors.forename: W
authors.initials: W
authors.lastname: Reuben
authors.forename: S
authors.initials: S
authors.lastname: Gnanakkan
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: L
authors.initials: L
authors.lastname: Barajas
authors.forename: V E
authors.initials: VE
authors.lastname: Eysselein
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D003106:Colon / Q000473:pathology; D016264:Dextran Sulfate; D004326:Drinking; D005260:Female; D020022:Genetic Predisposition to Disease; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout / Q000235:genetics*; D008817:Mice, Mutant Strains; D012016:Reference Values; D012996:Solutions; D016211:Transforming Growth Factor alpha / Q000172:deficiency / Q000235:genetics* / Q000494:pharmacology
chemical_list: D012996:Solutions; D016211:Transforming Growth Factor alpha; D016264:Dextran Sulfate