Variant form of diffuse corporal gastritis in NHE2 knockout mice

Mice lacking the NHE2 Na+/M+ gene develop gastritis of the glandular mucosa as early as the tenth day of life, achieving maximal intensity of inflamma tion from 17 to 19 days after birth and maximal atrophy at one year. We ass essed the effects of this process in such mice to 16 months of age. The sto mach of NHE2 null mutants was examined at 10, 17 to 20, 24 to 35 and 49 to 70 days, and at 12 to 16 months. The NHE2 wild-type (+/+) and NKE2 heterozy gous (+/-) mice were compared with the NHE2 homozygous mutant mice (-/-), T he stomach of the mutant mice at all ages was characterized by a substantia lly reduced number of parietal cells. The 16-day-old mouse stomach had a tr ansmural infiltrate of primarily neutrophils. With increasing age, neutroph ils were replaced by lymphocytes and plasma cells in the glandular mucosa o f the mutant mice. Young adult 49- to 70-day-old mice had surface cell hype rplasia and expansion of the replicating cell population. Hyperplasia of en terochromaffin-like cells and antral gastrin cells accompanied profound fun dic gland and surface cell hyperplasia, and became progressively more sever e with increasing age of the NHE2-/- mice. Neoplasms were not found in the mutant or control mice. This gastritis differs from that of autoimmune gast ritis in that it is transmural, begins in infancy, and is associated with a predominantly neutrophilic infiltrate in its early stages, Some of the his tologic changes in the adult mice can be explained on the basis of prolonge d achlorhydria, This mouse may be a suitable model for prolonged effects of achlorhydria.