Gastric Functions in Gastrin Gene Knock‐Out Mice

Abstract

The gastric hormone gastrin was the 2nd hormone to be identified and was initially recognized for its ability to induce acid secretion. Following the purification and subsequent development of specific radioimmunoassays for gastrin, it was also shown to be a regulator of oxyntic mucosal growth. To explore the importance of gastrin or its receptors for gastric development and gastric physiology both have been knocked out. The knock-out mice are viable, develop with any gross abnormalities, and are fertile. Even though gastrin acts as a growth factor during hypergastrinaemia there was no general atrophy of the gastrin mucosa in the knock-out mice. But the maturation of both parietal and ECL cells were disturbed and the number of parietal cells reduced. Furthermore, lack of gastrin impaired basal acid secretion and rendered the parietal cells unresponsive to histamine and acetylcholine, the other two major stimulators of gastric acid secretion. Despite the major changes in gastric physiology, the number of genes down-regulated in the gastrin knock-out mice is modest. The achlorhydria due to lack of gastrin also leads to bacterial overgrowth of the stomachs of the gastrin knockout mice, which could facilitate the development of gastric ulcer disease and cancer.

Effect of Essential Oils on the Oxyntopeptic Cells and Somatostatin and Ghrelin Immunoreactive Cells in the European Sea Bass (Dicentrarchus labrax) Gastric Mucosa

“…SOM acts as a potent inhibitor of gastric acid secretion. In gastrin gene knockout mice, a reduction in the number of parietal cells was observed, whereas the EEC number was not affected by gene deletion [ 84 , 85 , 86 , 87 ]. In our study, we showed an increase in SOM-IR cells in fish fed a diet supplemented with EOs.…”

Mouse models of endocrine tumors

“…Indeed, the absence of Rb protein caused by heterozygous germline mutation induces childhoodonset retinoblastoma in a high percentage of humans. Surprisingly, the same phenomenon in mice induced the development of pituitary carcinomas (Jacks et al 1992, Vooijs et al 1998, 2002. Similarly, the role of p19, encoded by Cdkn2b, as a tumor suppressor in regulating pituitary anterior lobe proliferation has been revealed by a conventional knockout mouse model of Cdkn2b, as these knockout mice developed multiple tumor types including PRL-, GH-and FSH-secreting PAs (Bai et al 2014).…”

“…Because of this, it is considered a valuable model of stomach GEP-NET development in combination with other agents, like H. pylori or H. felis. Strikingly, the genetic ablation of gastrin in the gastrin-deficient mice (Friis-Hansen et al 1998) also results in the development of spontaneous gastric cancer at few weeks of age (Friis-Hansen 2002), suggesting that any dysregulations of gastrin production may lead to oncogenic growth.…”

Mouse Models of Gastric Carcinogenesis

“…Gastrin, which is produced by G cells in the antral mucosa, is a crucial regulatory hormone in the gastric mucosa and can regulate cell division, invasion, angiogenesis, and anti-apoptotic activity at the transcriptional level 142,143. It functions to regulate acid secretion in response to feeding and in maintaining developmental epithelial cell homeostasis in the fundic and antral mucosa.…”