Impairment of gastric acid secretion and increase of embryonic lethality in <i>Foxq1-</i>deficient mice

Gastric acid secretion in normal (+/+) C57B1/6J mice and congeneic, mast cell-deficient (mi/mi) C57B1/6J mice was examined. The mast cell-deficient animals had approximately 50% of the normal quantity of gastric histamine and a blunted basal acid level and secretory response. These observations were noted despite the presence of parietal cells, which were normal in number and morphology. The H2-antagonist ranitidine inhibited basal acid secretion in both groups of animals. Exogenous histamine induced a significant secretory response in normal and mast cell-deficient groups, but only the secretory response in normal animals could be blocked by the H2-antagonist. Treatment of mast cell-deficient animals with histamine for seven consecutive days before stimulation did not restore the histamine response to the normal (+/+) levels. The normal animals demonstrated an acid secretory response to pentagastrin. Mast cell-deficient mice also responded to pentagastrin, but the response was less than that observed in the normal animals, and a significant difference was not evident in all experiments. Furthermore, simultaneous injection of mast cell-deficient animals with histamine and pentagastrin did not restore pentagastrin responsiveness to normal levels, although the histamine concentration used was sufficient to raise acid secretion to basal levels of normal mice. These results support the conclusion that non-mast cell histamine only partially contributes to basal gastric acid secretion and is insufficient to facilitate full parietal cell responsiveness. Furthermore, pentagastrin requires the presence of mast cells to elicit a maximal secretory response but can use non-mast cell histamine to activate the parietal cells for acid secretion.

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Impaired gastric acid secretion in gastrin-deficient mice

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1998.274.3.g561 ◽

1998 ◽

Vol 274 (3) ◽

pp. G561-G568 ◽

Cited By ~ 50

Author(s):

Lennart Friis-Hansen ◽

Frank Sundler ◽

Ying Li ◽

Patrick J. Gillespie ◽

Thomas L. Saunders ◽

...

Keyword(s):

Acid Secretion ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Histidine Decarboxylase ◽

Embryonic Stem ◽

Parietal Cells ◽

Gastric Glands ◽

Partial Restoration ◽

Ecl Cells ◽

Deficient Mice

To further understand the role of the peptide hormone gastrin in the development and function of the stomach, we have generated gastrin-deficient mice by gene targeting in embryonic stem cells. Mutant mice were viable and fertile, without obvious visible abnormalities. However, gastric function was severely affected by the loss of gastrin. Basal gastric acid secretion was abolished and could not be induced by histamine, carbachol, or gastrin. Histological analysis revealed alterations in the two cell types primarily involved in acid secretion, parietal and enterochromaffin-like (ECL) cells. Parietal cells were reduced in number with an accumulation of immature cells lacking H+-K+-adenosinetriphosphatase (H+-K+-ATPase). ECL cells were positioned closer to the base of the gastric glands, with markedly lower expression of histidine decarboxylase. Gastrin administration for 6 days reversed the effects of the gastrin deficiency, leading to an increase in the number of mature, H+-K+-ATPase-positive parietal cells and a partial restoration of acid secretion. The results show that gastrin is critically important for the function of the acid secretory system.

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ECL cells and gastric acid secretion in gastrin-deficient mice

Gastroenterology ◽

10.1016/s0016-5085(98)84616-7 ◽

1998 ◽

Vol 114 ◽

pp. A1135

Author(s):

D Chen ◽

T Koh ◽

C-M Zhao ◽

R Håkanson ◽

TC Wang

Keyword(s):

Acid Secretion ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Ecl Cells ◽

Deficient Mice

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Enhancement of gastric acid secretion by histamine in histidine decarboxylase-deficient mice

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)47604-x ◽

2000 ◽

Vol 82 ◽

pp. 31

Author(s):

Satoshi Tanaka ◽

Satoru Takahashi ◽

Hiroshi Ohtsu ◽

Takehiko Watanabe ◽

Susumu Okabe ◽

...

Keyword(s):

Acid Secretion ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Histidine Decarboxylase ◽

Deficient Mice

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I. Physiological studies with gastrin in transgenic mice

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1999.277.1.g6 ◽

1999 ◽

Vol 277 (1) ◽

pp. G6-G11 ◽

Cited By ~ 13

Author(s):

Timothy C. Wang ◽

Graham J. Dockray

Keyword(s):

Transgenic Mice ◽

Acid Secretion ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Parietal Cell ◽

Knockout Mice ◽

Recent Progress ◽

Cell Function ◽

Deficient Mice

The role of gastrin in the regulation of gastrointestinal growth and acid secretion has been addressed through recent studies involving transgenic and knockout mice. The role of gastrin as a key modulator of parietal cell function and gastric acid secretion has been confirmed through studies in mice deficient in either gastrin or the gastrin/CCK-B receptor. However, although gastrin-deficient mice show no changes in gastric proliferation, they do show reduced colonic proliferation, and rates of colonic proliferation are increased in transgenic mice overexpressing glycine-extended gastrin or progastrin. This themes article highlights recent progress in our understanding of the biology of gastrin through studies in genetically modified mice.

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