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Updated: Jun 11, 2026
Mouse Models Of Helicobacter Infection And Gastric Pathologies
Published on: October 18, 2018
Experimental Helicobacter marmotae infection in A/J mice causes enterohepatic disease
Mary M Patterson1, Arlin B Rogers1, James G Fox1
1Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Building 16-825, Cambridge, MA 02139, USA.
Abstract:
Helicobacter marmotae has been identified in the inflamed livers of Eastern woodchucks (Marmota monax) infected with woodchuck hepatitis virus (WHV), as well as from the livers of WHV-negative woodchucks. Because the majority of WHV-positive woodchucks with hepatic tumours were culture or PCR positive for this helicobacter, and WHV-negative woodchucks with H. marmotae had hepatitis, the bacterium may have a role in tumour promotion related to chronic inflammation. In this study, the type strain of H. marmotae was inoculated intraperitoneally into 48 male and female A/J mice, a strain noted to be susceptible to Helicobacter hepaticus-induced liver tumours. Sixteen mice served as mock-dosed controls. At 6, 12 and 18 months post-inoculation (p.i.), there were statistically significant (P<0.05) differences in mean inflammation scores for the caecum and proximal colon between experimentally infected and control mice. Differences in hepatic inflammation were significant (P<0.05) at 6 and 12 months p.i. between the two groups but not at the 18 month time point. Two infected male mice had livers with severe hepatitis, and the liver samples were culture positive for H. marmotae. Serum IgG levels in the mice dosed with H. marmotae were elevated for the duration of the study. These results demonstrate that the woodchuck helicobacter can successfully colonize mice and cause enterohepatic disease. In the future, a mouse-adapted strain of H. marmotae could be selected to maximize colonization and lesion development. Such a woodchuck helicobacter-infected mouse model could be used to dissect potential mechanisms of microbial co-carcinogenesis involved in tumour development in woodchucks with WHV and in humans with hepatitis B virus.
Insights
Helicobacter marmotae, a woodchuck bacterium, successfully colonized mice, causing inflammation in the gut and liver. This establishes a new mouse model for studying microbial co-carcinogenesis in liver diseases.
Area of Science:
- Microbiology
- Hepatology
- Gastroenterology
Background:
- Helicobacter marmotae is found in woodchuck livers, associated with woodchuck hepatitis virus (WHV) and hepatic tumors.
- Both WHV-positive and WHV-negative woodchucks with H. marmotae exhibit hepatitis, suggesting a role in chronic inflammation and tumor promotion.
Purpose of the Study:
- To investigate the pathogenicity of H. marmotae in a susceptible mouse model.
- To establish a mouse model for studying H. marmotae-induced enterohepatic disease and its potential role in co-carcinogenesis.
Main Methods:
- A/J mice were inoculated intraperitoneally with H. marmotae type strain.
- Control groups received a mock dose.
- Mice were monitored for 6, 12, and 18 months post-inoculation for inflammation, bacterial colonization, and serological changes.
Main Results:
- H. marmotae successfully colonized mice, inducing statistically significant inflammation in the caecum and proximal colon.
- Significant hepatic inflammation was observed at 6 and 12 months post-inoculation.
- Two infected mice developed severe hepatitis with positive H. marmotae cultures, and elevated serum IgG levels were noted throughout the study.
Conclusions:
- H. marmotae can colonize mice and induce enterohepatic disease, validating its use in a novel mouse model.
- This model can be utilized to explore mechanisms of microbial co-carcinogenesis in woodchuck hepatitis virus-associated liver tumors and human hepatitis B virus infections.
