Phenotypes of mice with invalidation of cholecystokinin (CCK(1) or CCK(2)) receptors.

Cholecystokinin (CCK) is a peptide originally discovered in the gastrointestinal tract, but also found in high density in the mammalian brain. This peptide has been shown to be involved in numerous physiological functions such as feeding behavior, central respiratory control and cardiovascular tonus, vigilance states, memory processes, nociception, emotional and motivational responses. CCK interacts with nanomolar affinites with two different receptors designated CCK(1) and CCK(2). Primarily, the functional role of these binding sites in the brain and the periphery has been investigated thanks to the development of potent and selective CCK receptor antagonists and agonists. However, several studies have yielded conflicting data. Knockout mice provide unique opportunities to analyse diverse aspects of gene function in vivo. This review highlights recent progress in our understanding of the role of CCK(1) and CCK(2) receptors obtained by using mice with genetic invalidation of CCK(1) or CCK(2) receptors or natural CCK receptors mutants. The limits of this approach is discussed and some results were compared to those obtained by pharmacological blockade of CCK receptors by selective antagonists.