Gastric Phenotypic Abnormality in Cholecystokinin 2 Receptor Null Mice

Gastrin, released from antral G-cells, plays an important role in the regulation of gastric acid secretion and is trophic for the stomach. The cholecystokinin type 2 (CCK)2 receptor (previously referred to as CCK-B/gastrin receptors) is expressed in both parietal cells and ECL cells in the oxyntic mucosa of stomach. Gastric phenotypic abnormality has been observed in CCK2 receptor null (gene knock-out) mice. Such mice displayed markedly impaired gastric acid secretion, atrophy of the oxyntic mucosa and hypergastrinaemia. The impaired acid secretion may be the result of a reduced parietal cell mass, a reduced proportion of actively secreting parietal cells (with secretory canaliculi), and a replacement of ECL cells by histamine-free ECL-like cells. The ECL-like cells, observed in the CCK2 receptor null mice, lacked the hallmark features of wild-type ECL cells, i.e. histamine and cytoplasmic secretory vesicles. However, they had the features of endocrine cells, such as the content of pancreastatin (a fragment of chromogranin A), with cytoplasmic small dense-core granules and microvesicles. We propose that the replacement of ECL cells by ECL-like cells in the mutant mice reflects an altered differentiation of the same precursors that develop into ECL cells in wild-type mice. Thus, studies of CCK2 receptor null mice demonstrate the importance of the receptor in the regulation of gastric acid secretion and in the differentiation of ECL cells in the oxyntic mucosa of stomach.