Abnormal gastric histology and decreased acid production in cholecystokinin-B/gastrin receptor-deficient mice.
OBJECTIVE
The cholecystokinin (CCK)-B/gastrin receptor is one of several regulators of gastric acid secretion and mucosal growth. To elucidate the contribution of this receptor relative to other trophic and secretory factors, mice that lack the CCK-B/gastrin receptor have been generated and studied.


METHODS
Both alleles of the CCK-B/gastrin receptor were inactivated by targeted gene disruption. Analysis of the mice included measurement of basal gastric pH and plasma gastrin levels. In addition, multiple gastric mucosal cell types were identified by immunostaining and quantified.


RESULTS
Homozygous mutant mice were viable, fertile, and appeared grossly normal into adulthood. The receptor-deficient mice exhibited a marked increase in basal gastric pH (from 3.2 to 5.2) and an approximately 10-fold elevation in plasma gastrin concentration compared with wild-type controls. In the stomach of mutant animals, parietal and enterochromaffin-like cells were decreased, providing a likely explanation for the reduction in acid output. In the antrum, a decrease in somatostatin cell density and an increase in the gastrin cell number were observed, consistent with the concomitant elevation in circulating gastrin.


CONCLUSIONS
Together, these findings demonstrate the importance of the CCK-B/gastrin receptor in maintaining the normal cellular composition and function of the gastric mucosa.
Langhans
N
N
Department of Pediatrics, Tupper Research Institute, New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA.
Rindi
G
G
Chiu
M
M
Rehfeld
J F
JF
Ardman
B
B
Beinborn
M
M
Kopin
A S
AS
D000818:Animals; D002455:Cell Division; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000473:pathology*; D005755:Gastrins / Q000097:blood; D005822:Genetic Vectors; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D010295:Parietal Cells, Gastric / Q000473:pathology; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
D005755:Gastrins; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin