Infection with Helicobacter pylori uniformly leads to a chronic superficial gastritis that may progress to atrophic gastritis, a premalignant process. A mouse model of Helicobacter felis infection was used to study possible genetic determinants of the response to infection.

Three inbred mouse strains with known secretory phospholipase A₂ (sPLA₂) genotypes [BALB/c (+/+), C3H/HeJ (+/+), and C57BL/6 (−/−)] were orally infected with H. felis and examined longitudinally using routine histology, immunocytochemistry, electron microscopy, proliferating cell nuclear antigen, terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling, and Northern and Western blot studies.

Only the C57BL/6 strain showed increased gastric fundic proliferation and apoptosis in response to infection. In addition, the C57BL/6 mouse showed a marked loss of parietal and chief cells, along with a marked expansion of an aberrant gastric mucous cell lineage that stained positive for spasmolytic polypeptide. In contrast, no significant change in these cell types was observed in BALB/c and C3H/HeJ strains. Increased expression of sPLA₂ was observed in BALB/c and C3H/HeJ after H. felis infection, whereas sPLA₂ expression was absent in C57BL/6 mice.

H. felis infection leads to increased apoptosis and altered cellular differentiation in the C57BL/6 mouse, a strain that lacks gastric sPLA₂ expression. Because sPLA₂ has been identified recently as the MOM1 (modifier of MIN) locus that influences polyp formation in the colon, these studies suggest that sPLA₂ may also influence the gastric epithelial response to Helicobacter infection. GASTROENTEROLOGY 1998;114:675-689