Genetically engineered mice: a new paradigm to study gastric physiology.
OBJECTIVE
To summarize key aspects from recent research as well as review articles on the topic of genetic mouse models, particularly in knockout mice, that have considerably contributed to understanding the pathways and mechanisms underlying gastric physiology.


RESULTS
A series of knockout mouse models has proven to be invaluable in elucidating the mechanism and validating the current model of acid secretion. The interaction between the gastrin-histamine and cholecystokinin-somatostatin pathways was identified using the genetic approach as being critical in regulating acid secretion. Curiously, neither ghrelin nor ghrelin receptor knockout mice displayed the expected lean phenotype. Importantly, the study of obestatin in GPR39 knockout mice could be misleading, as zinc rather than obestatin is the endogenous ligand for GPR39. The physiological roles of ghrelin and obestatin have yet to be confirmed using knockout mouse models.


CONCLUSIONS
The knockout mouse continues to serve as an excellent model to dissect the complexity of the mechanism of gastric acid secretion and to study the physiological importance of gastric ghrelin.
Chen
Duan
D
Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway. duan.chen@ntnu.no
Zhao
Chun-Mei
CM
D000818:Animals; D005744:Gastric Acid / Q000378:metabolism; D054439:Ghrelin / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D010295:Parietal Cells, Gastric / Q000502:physiology; D013270:Stomach / Q000502:physiology*
D054439:Ghrelin