III. Lessons learned from gastrin gene deletion in mice

Abstract

Gastrin is the principal hormonal inducer of gastric acid secretion. Chronic hypergastrinemia, leading to hypersecretion of gastric acid and increased proliferation of parietal and enterochromaffin-like (ECL) cells, has been well described. In contrast, the physiological consequences of chronic gastrin deficiency had been poorly understood until the recent genetic engineering of mouse mutants containing a gastrin gene deletion by homologous recombination in embryonic stem cells. This themes article describes the consequences of constitutive gastrin deficiency on the development and physiology of the stomach. A lack of gastrin disrupts basal gastric acid secretion and renders the acid secretory system unresponsive to acute histaminergic, cholinergic, and gastrinergic stimulation. The defect in acid secretion is greater than would have been predicted from previous studies in which gastrin action was acutely blocked. Cellular changes include thinning of the gastric mucosa in the gastrin-deficient mice, with a reduction in parietal cells and reduced expression of markers of parietal and ECL cell-differentiated functions. The results suggest that gastrin is required for the functional maturation of the acid-secretory system.

Characteristics of the Cholecystokinin-Induced Depolarization of Pacemaking Activity in Cultured Interstitial Cells of Cajal from Murine Small Intestine

“…In humans, strong evidence suggests that CCK 1 activation is involved in the regulation of numerous physiological processes, including gallbladder contraction, relaxation of the sphincter of Oddi, stimulation of pancreatic secretion, slowing of colonic motility regulation of satiety, reduced esophageal sphincter relaxation, and in the inhibitions of gastric emptying and acid secretion [35,36,37,38,39,40,41,42,43,44,45,46]. Although several authors have shown that the CCK 1 is relevant in various GI diseases, the role played by CCK 1 under these conditions has not been firmly established [35,47].…”

The ontogeny and developmental physiology of gastric acid secretion

“…Nonetheless, gastrin deficiency not only has physiologic effects, but also alters mucosal histology. Gastrin-deficient mice have a profound impairment in basal and stimulated acid secretion [8]. The absence of gastrin also leads to a reduction in the thickness of the mucosa [9], and while all major epithelial cell types are present, there are profound changes in the proportion and distribution of the cells.…”