Mice carrying a truncated Apc gene have diminished gastric epithelial proliferation, gastric inflammation, and humoral immunity in response to Helicobacter felis infection.
Helicobacter pylori infection and adenomatous polyposis coli (Apc) gene mutations have been linked to gastric cancer in humans, but possible synergistic interaction(s) between these risk factors have not been examined. Fourteen C57BL/6 wild-type and 14 Apc1638 heterozygous mice were inoculated with Helicobacter felis at 6 weeks of age and compared at various time points with a similar number of uninfected control mice of the same genotype. Both infected and uninfected Apc1638 mice had a limited incidence of atypical proliferation foci in the mucosa of the antrum and pyloric junction at 4.5 and 6 months of age, whereas polyps of the antrum and pylorus were present in all mice, regardless of infection status, at 7.5 months. In contrast, no altered gastric mucosal foci were observed in control or infected C57BL/6 mice at any time point. Interestingly, the infected Apc1638 mice had less epithelial proliferation and inflammation in the body of the stomach, lower anti-H. felis serum IgG antibody responses (although both the wild-type and Apc 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 antrum and pyloric junction, but H. felis infection of the Apc mutant mouse does not lead to an increased rate of gastric neoplasia. In addition, our data suggest this Apc mutation may actually lead to decreased immune, inflammatory, and gastric hyperplastic responses to Helicobacter infection, suggesting the possibility of a novel role for this tumor suppressor gene in the immune and local tissue responses to gastric bacterial infection.
Fox
J G
JG
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge 02138, USA.
Dangler
C A
CA
Whary
M T
MT
Edelman
W
W
Kucherlapati
R
R
Wang
T C
TC
D025601:Adenomatous Polyposis Coli Protein; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000917:Antibody Formation; D003598:Cytoskeletal Proteins / Q000502:physiology*; D005753:Gastric Mucosa / Q000166:cytology / Q000201:enzymology / Q000473:pathology; D017491:Genes, APC; D016998:Helicobacter / Q000276:immunology; D016481:Helicobacter Infections / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011127:Polyps / Q000382:microbiology; D015398:Signal Transduction; D013997:Time Factors; D014510:Urease / Q000378:metabolism
D025601:Adenomatous Polyposis Coli Protein; D000907:Antibodies, Bacterial; D003598:Cytoskeletal Proteins; D014510:Urease