MICE CARRYING A TRUNCATED APC GENE HAVE DIMINISHED GASTRIC EPITHELIALPROLIFERATION, GASTRIC INFLAMMATION, AND HUMORAL IMMUNITY IN RESPONSETO HELICOBACTER-FELIS INFECTION

Helicobacter pylori infection and adenomatous polyposis coli (Apc) gen e mutations have been linked to gastric cancer in humans, but possible synergistic interaction(s) between these risk factors have not been e xamined, Fourteen C57BL/6 wild-type and 14 Apc1638 heterozygous mice w ere inoculated with Helicobacter felis at 6 weeks of age and compared at various time points with a similar number of uninfected control mic e of the same genotype. Both infected and uninfected Apc1638 mice had a limited incidence of atypical proliferation foci in the mucosa of th e antrum and pyloric junction at 4.5 and 6 months of age, whereas poly ps of the antrum and pylorus were present in all mice, regardless of i nfection status, at 7.5 months, In contrast, no altered gastric mucosa l foci were observed in control or infected C57BL/6 mice at any time p oint. Interestingly, the infected Apc1638 mice had Less epithelial pro liferation and inflammation in the body of the stomach, lower anti-H. felis serum IgG antibody responses (although both the wild-type and Ap e mutant mice had a Th1-like immune response, based on a predominantly IgG2a immunoglobulin response), and higher bacteria and urease scores than did infected wild-type C57BL/6 mice, In conclusion, the Apc1638 truncating mutation leads to gastric dysplasia and polyposis of the an trum and pyloric junction, but H. felis infection of the Apc mutant mo use does not lead to an increased rate of gastric neoplasia, In additi on, our data suggest this Apc mutation may actually lead to decreased immune, inflammatory, and gastric hyperplastic responses to Helicobact er infection, suggesting the possibility of a novel role for this tumo r suppressor gene in the immune and local tissue responses to gastric bacterial infection.