Hypertrophic gastropathy in Helicobacter felis-infected wild-type C57BL/6 mice and p53 hemizygous transgenic mice.
OBJECTIVE
Helicobacter pylori infection causes gastritis and peptic ulcers and is linked epidemiologically to gastric cancer. To analyze host genetic factors and the influence of Helicobacter on cell proliferation, we used an inbred and p53 hemizygous mouse model of Helicobacter felis-induced gastritis.


METHODS
H. felis was inoculated by gastric intubation into SPF C57BL/6 wild-type and p53 hemizygous mice that were followed up for 1 year and compared with uninfected controls of the same genotype using histology, proliferating cell nuclear antigen (PCNA) staining, and 5-bromo-2'-deoxyuridine (BrdU) analysis.


RESULTS
Infected animalls developed sustained anti-H. felis serum immunoglobulin G antibody responses. Six months after infection, both wild-type and p53 hemizygous mice showed active chronic inflammation and marked mucosal hyperplasia compared with uninfected controls. One year after infection with H. felis, the wild-type and p53 hemizygous mice showed severe adenomatous and cystic hyperplasia of the surface foveolar epithelium. BrdU uptake and PCNA staining were markedly increased in both sets of infected mice compared with controls. Infected p53 hemizygous mice had a higher proliferative index than the infected wild-type mice.


CONCLUSIONS
H. felis can induce a hypertrophic gastropathy in the C57BL/6 genotype; loss of one p53 allele, although insufficient to initiate carcinogenesis at 1 year, enhances the proliferative index, which may lead to an increased risk of cancer induction.
Division of Comparative Medicine, Massachusetts Institute of Technology, Boston, USA.
J G
JG
Fox
X
X
Li
R J
RJ
Cahill
K
K
Andrutis
A K
AK
Rustgi
R
R
Odze
T C
TC
Wang
D000483:Alleles; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology; D005756:Gastritis / Q000382:microbiology* / Q000473:pathology*; D016158:Genes, p53; D016998:Helicobacter / Q000276:immunology; D016481:Helicobacter Infections; D006984:Hypertrophy; D007074:Immunoglobulin G / Q000032:analysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013270:Stomach / Q000473:pathology*
D000907:Antibodies, Bacterial; D007074:Immunoglobulin G