The
gastrointestinal hormone,
gastrin, was discovered a century ago as the second
hormone in history. Subsequently,
gastrin peptides have been identified and the genes encoding the
hormone as well as its receptor have been cloned in several mammalian species including the mouse. This has facilitated the development of
gastrin and
gastrin receptor deficient mice as models for genetic dissection of the role of
gastrins in maintaining gastric homeostasis and control of
acid secretion. The
gastrin knockout mice are achlorhydric due to inactivation of the ECL and parietal cells. Moreover, this
achlorhydria is associated with the development of intestinal
metaplasia and bacterial overgrowth, which ultimately lead to development of gastric
tumors. Outside the stomach,
gastrin deficiency alters pancreatic islet physiology and is associated with a moderate
fasting hypoglycemia in the fasting state. But lack of
gastrin does not impair islet regeneration. The association between
progastrin,
progastrin-derived processing intermediates and colorectal
carcinogenesis has also been examined through genetic or chemical
cancer induction in several mouse models, although the clinical relevance of these studies still remains to be proven. While others have focused on models of increased
gastrin production, the present review will describe the lessons learned from the
gastrin deficient mice. These mice help understand how dysregulation of
gastrin secretion may be implicated in human disease.