PT  - JOURNAL ARTICLE
AU  - Egger, B
AU  - Carey, H V
AU  - Procaccino, F
AU  - Chai, N-N
AU  - Sandgren, E P
AU  - Lakshmanan, J
AU  - Buslon, V S
AU  - French, S W
AU  - Büchler, M W
AU  - Eysselein, V E
TI  - Reduced susceptibility of mice overexpressing transforming growth factor α to dextran sodium sulphate induced colitis
AID  - 10.1136/gut.43.1.64
DP  - 1998 Jul 01
TA  - Gut
PG  - 64--70
VI  - 43
IP  - 1
4099  - http://gut.bmj.com/content/43/1/64.short
4100  - http://gut.bmj.com/content/43/1/64.full
SO  - Gut1998 Jul 01; 43
AB  - Background—Transforming growth factor α (TGF-α) knockout mice have increased susceptibility to dextran sodium sulphate (DSS) induced colitis. Aim—To substantiate the findings that TGF-α is a key mediator of colonic mucosal protection and/or repair mechanisms by evaluating the susceptibility of mice overexpressing TGF-α to DSS induced colitis. Methods—TGF-α overexpression was induced in transgenic mice by ZnSO4administration in drinking water (TG+). Three groups were used as controls: one transgenic group without ZnSO4 administration (TG−), and two non-transgenic littermate groups receiving ZnSO4 (Non-TG+) or only water (Non-TG−). Acute colitis was induced in all groups by administration of DSS (5%, w/v) in drinking water for six days ad libitum. Results—About 35–39% of the entire colonic mucosa was destroyed in Non-TG−, Non-TG+, and TG− animals compared with 9% in TG+ mice. The crypt damage score was 18.7 (0.9), 18.2 (1.0), 18.9 (0.8), and 6.8 (1.5) (means (SEM)) in Non-TG−, Non-TG+, TG−, and TG+ mice respectively. Mucin and bromodeoxyuridine staining were markedly enhanced in colons of TG+ mice compared with controls, indicating increased mucosal protection and regeneration. Conclusions—The significantly reduced susceptibility of mice overexpressing TGF-α to DSS further substantiates that endogenous TGF-α is a pivotal mediator of protection and/or healing mechanisms in the colon.