Fundic Gland Cysts in Atp4a-/- Mice Mimic Fundic Gland Polyps in Humans

Background: Innumerable fundic gland polyps (FGPs) (that is massive FGP polyposis) may be found in the human stomach. Innumerable fundic gland cysts (FGCs) develop in mice lacking the gene Atp4a (Atp4a((-/-))), that encodes the enzyme ATPase. The aim was to monitor the evolution of FGCs in Atp4a((-/-)) mice. Materials and Methods: Six pairs (male-female) of Atp4a((-/-)) mice, 8, 12 and 20 months old, were investigated. Wild-type Atp4a((+/+)) mice were used as controls. Results: In Atp4a((-/-)) female mice, the mucosal thickness increased both at 8 months (943 +/- 72 mm) (p<0.02) and at 12 months (p<0.0008) and even further at 20 months (p<0.0001). The FGC area was 13.183 +/- 7.218 mm(2) at 12 months and 73.361 +/- 50.591 mm(2) at 20 months (p<0.0008). FGCs in Atp4a((-/-)) mice were lined by parietal cells, mucous pit-foveolar cells and chief cells, thus mimicking FGPs in humans. Conclusion: Older female Atp4a((-/-)) mice developed innumerable FGCs, a phenomenon very similar to massive FGPs seen in humans. In the light of these similarities, the Atp4a((-/-)) mouse emerges as a suitable animal model to investigate the series of events taking place during the evolution of FGPs in humans.