MICE LACKING TRANSFORMING-GROWTH-FACTOR-ALPHA HAVE AN INCREASED SUSCEPTIBILITY TO DEXTRAN SULFATE-INDUCED COLITIS

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 preser ving the integrity of the colon, Methods: Colitis was induced by oral administration of dextran sodium sulfate (DSS, 5 g/dL) to knockout mic e, their genetic controls (GC), wad mice, and BALB/c mice. TGF-alpha w as also administered intraperitoneally to wa-1 mice to evaluate the ef fect of exogenous TGF-alpha in DSS colitis. Results: In response to DS S, nearly 60% of the entire colonic mucosa was destroyed in knockout a nd wa-1 mice, compared with 22% in GC mice and 16% in BALB/c mice, Bod y weight loss was doubled in knockout (28%) and wa-1 mice (23%) compar ed 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 wit h controls, Conclusions: The marked susceptibility of TGF-alpha knocko ut and wa-1 mice to DSS and the obvious amelioration of the colonic in jury by exogenous TGF-alpha application in wa-1 mice suggest that TGF- alpha is a mediator of protection and/or healing mechanisms in the col on.