ABNORMAL GASTRIC HISTOLOGY AND DECREASED ACID PRODUCTION IN CHOLECYSTOKININ-B GASTRIN RECEPTOR-DEFICIENT MICE/

Background & Aims: The cholecystokinin (CCK)-B/gastrin receptor is one of several regulators of gastric acid secretion and mucosal growth, T o elucidate the contribution of this receptor relative to other trophi c and secretory factors, mice that lack the CCK-B/gastrin receptor hav e been generated and studied, Methods: Both alleles of the CCK-B/gastr in receptor were inactivated by targeted gene disruption, Analysis of the mice included measurement of basal gastric pH and plasma gastrin l evels, In addition, multiple gastric mucosal cell types were identifie d by immunostaining and quantified. Results: Homozygous mutant mice we re viable, fertile, and appeared grossly normal Into adulthood, The re ceptor-deficient mice exhibited a marked increase in basal gastric pH (from 3.2 to 5.2) and an similar to 10-fold elevation in plasma gastri n concentration compared with wild-type controls, In the stomach of mu tant animals, parietal and enterochromaffin-like cells were decreased, providing a likely explanation for the reduction in acid output, in t he antrum, a decrease in somatostatin cell density and an increase in the gastrin cell number were observed, consistent with the concomitant elevation in circulating gastrin, Conclusions: Together, these findin gs demonstrate the importance of the CCK-B/gastrin receptor in maintai ning the normal cellular composition and function of the gastric mucos a.