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Updated: Jun 15, 2026
Murine Colitis Modeling using Dextran Sulfate Sodium (DSS)
Published on: January 19, 2010
Atm-deficient mice exhibit increased sensitivity to dextran sulfate sodium-induced colitis characterized by elevated
Aya M Westbrook1, Robert H Schiestl
1Molecular Toxicology Interdepartmental Program, University of California at Los Angeles School of Medicine, Los Angeles, California 90095, USA.
Abstract:
The role of ataxia telangiectasia mutated (ATM), a DNA double-strand break recognition and response protein, in inflammation and inflammatory diseases is unclear. We have previously shown that high levels of systemic DNA damage are induced by intestinal inflammation in wild-type mice. To determine the effect of Atm deficiency in inflammation, we induced experimental colitis in Atm(-/-), Atm(+/-), and wild-type mice via dextran sulfate sodium (DSS) administration. Atm(-/-) mice had higher disease activity indices and rates of mortality compared with heterozygous and wild-type mice. Systemic DNA damage and immune response were characterized in peripheral blood throughout and after three cycles of treatment. Atm(-/-) mice showed increased sensitivity to levels of DNA strand breaks in peripheral leukocytes, as well as micronucleus formation in erythroblasts, compared with heterozygous and wild-type mice, especially during remission periods and after the end of treatment. Markers of reactive oxygen and nitrogen species-mediated damage, including 8-oxoguanine and nitrotyrosine, were present both in the distal colon and in peripheral leukocytes, with Atm(-/-) mice manifesting more 8-oxoguanine formation than wild-type mice. Atm(-/-) mice showed greater upregulation of inflammatory cytokines and significantly higher percentages of activated CD69+ and CD44+ T cells in the peripheral blood throughout treatment. ATM, therefore, may be a critical immunoregulatory factor dampening the deleterious effects of chronic DSS-induced inflammation, necessary for systemic genomic stability and homeostasis of the gut epithelial barrier.
Insights
Ataxia telangiectasia mutated (ATM) deficiency exacerbates experimental colitis, increasing mortality and DNA damage. ATM plays a crucial role in regulating immune responses and maintaining genomic stability during inflammation.
Area of Science:
- Genetics
- Immunology
- Molecular Biology
Background:
- The role of Ataxia Telangiectasia Mutated (ATM) in inflammation is not well understood.
- Previous research indicated systemic DNA damage during intestinal inflammation in wild-type mice.
Purpose of the Study:
- To investigate the impact of ATM deficiency on experimental colitis.
- To assess the role of ATM in systemic DNA damage and immune responses during inflammation.
Main Methods:
- Experimental colitis was induced in Atm(-/-), Atm(+/-), and wild-type mice using dextran sulfate sodium (DSS).
- Disease activity, mortality, systemic DNA damage (micronucleus formation, 8-oxoguanine, nitrotyrosine), and immune cell activation (CD69+, CD44+ T cells) were monitored.
Main Results:
- Atm(-/-) mice exhibited higher mortality and disease activity indices compared to controls.
- ATM-deficient mice showed increased sensitivity to DNA strand breaks and oxidative damage markers.
- Greater upregulation of inflammatory cytokines and T cell activation was observed in Atm(-/-) mice.
Conclusions:
- ATM acts as a critical immunoregulatory factor, mitigating the detrimental effects of chronic DSS-induced inflammation.
- ATM is essential for maintaining systemic genomic stability and gut epithelial barrier homeostasis.
