Mice lacking transforming growth factor alpha have an increased susceptibility to dextran sulfate-induced colitis.
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.
Egger
B
B
Inflammatory Bowel Disease Center, Harbor-UCLA Medical Center, Torrance, USA.
Procaccino
F
F
Lakshmanan
J
J
Reinshagen
M
M
Hoffmann
P
P
Patel
A
A
Reuben
W
W
Gnanakkan
S
S
Liu
L
L
Barajas
L
L
Eysselein
V E
VE
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
D012996:Solutions; D016211:Transforming Growth Factor alpha; D016264:Dextran Sulfate