Atrophic gastritis is associated with anti‐parietal cell antibodies in Ctox7 transgenic mice

The Ctox7 transgenic mouse model is characterized by a progressive atrophic gastritis resulting from expression of the cholera toxin A1 subunit in parietal cells with the H + , K + ‐ATPase β‐subunit promoter. As Ctox7 mice age they develop a cellular transformation of the oxyntic mucosa, including expanded mucous neck cells, and loss of parietal and chief cells. These are standard cellular features of atrophic gastritis, which can be caused by autoimmune destruction of the gastric epithelium. Accordingly we tested Ctox7 plasma for anti‐parietal cell antibodies. A proportion of the Ctox7 transgenics contained autoantibodies with increased incidence as the mice aged. In contrast, autoantibodies were not detected in nontransgenic controls. A group of 29 Ctox7 mice 6–14 mo. of age were examined for anti‐parietal cell antibodies and histological evidence of inflammation. Large lymphoid follicles penetrating the oxyntic mucosa were observed in mice containing autoantibodies. Plasma cells were readily observed in the inflammatory infiltrates in these mice. Other Ctox7 mice that did not have anti‐parietal cell antibodies were observed with less severe inflammatory infiltrates, suggesting that the cellular response can be dissociated from the humoral response and may precede autoantibody development. Atrophic gastritis is associated with gastric tumor development in human. Accordingly, we have observed gastric tumor nodules in Ctox7, with dysplasia, mucus‐filled cysts and increased proliferation. Our data suggests that Ctox7 is a new mouse model of autoimmune gastritis. This research was supported by NIH.