SPONTANEOUS INFLAMMATORY BOWEL-DISEASE IN MULTIPLE MUTANT MOUSE LINES- ASSOCIATION WITH COLONIZATION BY HELICOBACTER-HEPATICUS

Background. Both genetic and microbial factors are thought to play a r ole in the development of inflammatory bowel disease (IBD): however, n o causative microbial agent has been clearly defined for humans or ani mals. Normal flora or previously unrecognized intestinal pathogens may contribute to the development of disease in susceptible hosts. A newl y recognized murine Helicobacter, H. hepaticus, causes hepatitis in mi ce and in one strain of mice is linked to liver cancer. This study inv estigates 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 no ted clinically in multiple genetically altered mouse lines was evaluat ed for the presence of H. hepaticus and histologic evidence of IBD. Fi fty-five mice representing 11 different genetic alterations were evalu ated. Results. H. hepaticus was detected in 85% of mutant mice with re ctal 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. C onclusion. The presence of H. hepaticus in association with IBD in mul tiple lines of genetically altered mice suggests further studies are n eeded to test experimentally the role H. hepaticus plays in the develo pment of IBD in susceptible mice. Additionally, specific mutant mouse lines infected with H. hepaticus is in this study may provide addition al models for elucidation of microbial and genetic factors in the path ogenesis of IBD.