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Spontaneous inflammatory bowel disease in multiple mutant mouse lines: association with colonization by Helicobacter
1Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge 02139, USA.
Background:
Both genetic and microbial factors are thought to play a role in the development of inflammatory bowel disease (IBD): however, no causative microbial agent has been clearly defined for humans or animals. Normal flora or previously unrecognized intestinal pathogens may contribute to the development of disease in susceptible hosts. A newly recognized murine Helicobacter, H. hepaticus, causes hepatitis in mice and in one strain of mice is linked to liver cancer. This study investigates the association between colonization of the lower intestinal tract of multiple genetically altered lines of mice with H. hepaticus, and the occurrence of IBD.
Materials And Methods:
Rectal prolapse noted clinically in multiple genetically altered mouse lines was evaluated for the presence of H. hepaticus and histologic evidence of IBD. Fifty-five mice representing 11 different genetic alterations were evaluated.
Results:
H. hepaticus was detected in 85% of mutant mice with rectal prolapse. Histologic evidence of proliferative typhlitis, colitis or proctitis was present in 65% of the animals examined, 89% of which were positive for H. hepaticus as detected by species specific PCR.
Conclusion:
The presence of H. hepaticus in association with IBD in multiple lines of genetically altered mice suggests further studies are needed to test experimentally the role H. hepaticus plays in the development of IBD in susceptible mice. Additionally, specific mutant mouse lines infected with H. hepaticus in this study may provide additional models for elucidation of microbial and genetic factors in the pathogenesis of IBD.
Insights
A new study links Helicobacter hepaticus (H. hepaticus) to inflammatory bowel disease (IBD) in genetically altered mice. This bacterium was found in most mice with IBD, suggesting it may play a role in disease development.
Area of Science:
- Microbiology
- Gastroenterology
- Immunology
Background:
- Inflammatory bowel disease (IBD) is influenced by genetic and microbial factors, but a specific cause remains undefined.
- A novel bacterium, Helicobacter hepaticus (H. hepaticus), is known to cause hepatitis and liver cancer in mice.
- This research explores the connection between H. hepaticus colonization and IBD in genetically modified mouse models.
Purpose of the Study:
- To investigate the association between H. hepaticus and IBD in genetically altered mice.
- To determine if H. hepaticus is present in mice exhibiting IBD symptoms like rectal prolapse.
Main Methods:
- Evaluated 55 mice from 11 genetically altered lines exhibiting rectal prolapse.
- Assessed mice for the presence of H. hepaticus using species-specific PCR.
- Examined rectal tissue for histologic evidence of IBD (typhlitis, colitis, proctitis).
Main Results:
- H. hepaticus was detected in 85% of mutant mice with rectal prolapse.
- Histologic evidence of IBD was found in 65% of the examined mice.
- Of the mice with IBD, 89% tested positive for H. hepaticus.
Conclusions:
- The co-occurrence of H. hepaticus and IBD in multiple genetically altered mouse lines warrants further investigation.
- These mouse models can aid in understanding the interplay of microbial and genetic factors in IBD pathogenesis.
- Experimental studies are needed to confirm the causal role of H. hepaticus in IBD development in susceptible mice.