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Murine Colitis Modeling using Dextran Sulfate Sodium (DSS)
Published on: January 20, 2010
Reduced susceptibility of mice overexpressing transforming growth factor alpha to dextran sodium sulphate induced
B Egger1, H V Carey, F Procaccino
1Inflammatory Bowel Disease Center, Harbor-UCLA Medical Center, Torrance 90509, USA.
Background:
Transforming growth factor alpha (TGF-alpha) knockout mice have increased susceptibility to dextran sodium sulphate (DSS) induced colitis.
Aim:
To substantiate the findings that TGF-alpha is a key mediator of colonic mucosal protection and/or repair mechanisms by evaluating the susceptibility of mice overexpressing TGF-alpha to DSS induced colitis.
Methods:
TGF-alpha overexpression was induced in transgenic mice by ZnSO4 administration 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 and 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-alpha to DSS further substantiates that endogenous TGF-alpha is a pivotal mediator of protection and/or healing mechanisms in the colon.
Insights
Mice overexpressing transforming growth factor alpha (TGF-alpha) showed significantly reduced susceptibility to dextran sodium sulphate (DSS)-induced colitis, highlighting TGF-alpha's role in colon protection and repair.
Area of Science:
- Gastroenterology
- Immunology
- Molecular Biology
Background:
- Transforming growth factor alpha (TGF-alpha) knockout mice exhibit heightened susceptibility to dextran sodium sulphate (DSS)-induced colitis.
- This suggests a crucial role for TGF-alpha in colonic mucosal defense and regeneration.
Purpose of the Study:
- To confirm TGF-alpha's role as a key mediator in colonic mucosal protection and repair.
- To evaluate the susceptibility of mice overexpressing TGF-alpha to DSS-induced colitis.
Main Methods:
- TGF-alpha overexpression was induced in transgenic mice (TG+) via ZnSO4 in drinking water.
- Controls included transgenic mice without ZnSO4 (TG-), and non-transgenic mice with (Non-TG+) or without (Non-TG-) ZnSO4.
- Acute colitis was induced using 5% DSS in drinking water for six days.
Main Results:
- Mice overexpressing TGF-alpha (TG+) experienced significantly less colonic mucosal destruction (9%) compared to controls (35-39%).
- The crypt damage score was substantially lower in TG+ mice (6.8) versus controls (18.2-18.9).
- Enhanced mucin and bromodeoxyuridine staining in TG+ mice indicated improved mucosal protection and regeneration.
Conclusions:
- Overexpression of TGF-alpha significantly reduces susceptibility to DSS-induced colitis.
- These findings strongly support TGF-alpha as a pivotal endogenous mediator of colonic protection and healing mechanisms.

