TY - JOUR

T1 - Gastric functions in gastrin gene knock-out mice

AU - Friis-Hansen, Lennart

PY - 2002/12/1

Y1 - 2002/12/1

N2 - 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 knock-out mice, which could facilitate the development of gastric ulcer disease and cancer.

AB - 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 knock-out mice, which could facilitate the development of gastric ulcer disease and cancer.

UR - http://www.scopus.com/inward/record.url?scp=0036965515&partnerID=8YFLogxK

U2 - 10.1034/j.1600-0773.2002.910614.x

DO - 10.1034/j.1600-0773.2002.910614.x

M3 - Journal article

C2 - 12688380

AN - SCOPUS:0036965515

VL - 91

SP - 363

EP - 367

JO - Pharmacology and Toxicology

JF - Pharmacology and Toxicology

SN - 0901-9928

IS - 6

ER -