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Am J Physiol Regul Integr Comp Physiol 294: R803-R810, 2008. First published December 26, 2007; doi:10.1152/ajpregu.00682.2007
0363-6119/08 $8.00
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GENETICALLY MODIFIED ANIMALS AND MODEL ORGANISMS

Characterization of mice lacking the gene for cholecystokinin

Chun-Min Lo,1 Linda C. Samuelson,3 James Brad Chambers,2 Alexandra King,1 Justin Heiman,2 Ronald J. Jandacek,1 Randall R. Sakai,2 Stephen C. Benoit,2 Helen E. Raybould,4 Stephen C. Woods,2 and Patrick Tso1

1Departments of Pathology and Laboratory Medicine and 2Psychiatry, University of Cincinnati, Genome Research Institute, Cincinnati, Ohio; 3Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan; and 4Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, California

Submitted 21 September 2007 ; accepted in final form 21 December 2007

CCK acts peripherally as a satiating peptide released during meals in response to lipid feeding and centrally functions in the modulation of feeding, exploratory, and memory activities. The present study determined metabolic parameters, food intake, anxiety-like behaviors, and cognitive function in mice lacking the CCK gene. We studied intestinal fat absorption, body composition, and food intake of CCK knockout (CCK-KO) mice by using the noninvasive measurement of intestinal fat absorption along with quantitative magnetic resonance (QMR) imaging and the DietMax system, respectively. Additionally, exploratory and memory capacities were assessed by monitoring running wheel activity and conducting elevated plus-maze and Morris water-maze tests with these mice. Compared with wild-type (WT) littermate controls, CCK-KO mice had normal food intake, fat absorption, body weight, and body mass. CCK-KO mice ate more food than control animals during the light period and less food during the dark period. Energy expenditure was unchanged between the genotypes; however, CCK-KO mice displayed greater fatty acid oxidation. CCK-KO mice were as active as WT animals in the running wheel test. CCK-KO mice spent more time in the closed arms of an elevated plus-maze, indicative of increased anxiety. Additionally, CCK-KO mice exhibited attenuated performance in a passive avoidance task and impaired spatial memory in the Morris water maze test. We conclude that CCK is involved in metabolic rate and is important for memory and exploration. CCK is intimately involved in multiple processes related to cognitive function and food intake regulation.

cholecystokinin 1 receptor; cholecystokinin 2 receptor; cognitive behaviors


Address for reprint requests and other correspondence: P. Tso, Dept. of Pathology and Laboratory Medicine, Univ. of Cincinnati, 2120 E. Galbraith Rd., Bldg. A, ML 0507, Cincinnati, OH 45237 (e-mail: tsopp{at}email.uc.edu)






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