Understanding corticotropin releasing factor neurobiology: contributions from mutant mice

Mice with transgenic expression or deletion of the CRF peptide, transgenic expression of the CRF-BP or deletion of specific CRF receptor subtypes exist and will be valuable for examining candidate mediators in animal model systems recapitulating a variety of normal function. In particular, results described in this review implicate CRF in acute emotional responses studied in animal models of anxiety and drug abstinence. CRF also appears to play a role in behavioral and physiological plasticity judging by alterations in HPA reactivity to stress, information processing and energy balance regulation in CRF mutant models. Accordingly, the creation of genetically engineered mice now permits the evaluation of contributory roles for several CRF-related gene products in the pathophysiology of a variety of complex behavioral disorders. For example, the postulated causal linkage between overactivation of CRF systems and the hyper-emotionality which characterizes human affective disorders can now be more thoroughly evaluated by examining the phenotype of CRF mutant mice in animal models of depression, dementia and substance abuse.