Targeted mutations of the corticotropin-releasing factor system: effects on physiology and behavior.

Genetic modifications of the genes that encode proteins integral to the corticotropin-releasing factor (CRF) system have been employed in the creation of mutant mice that serve as tools for studying the role of this neuropeptide in regulated and dysregulated behaviors and physiology. Overexpression of the CRF peptide and CRF binding protein as well as deletion of the peptide, binding protein, and both known receptors has been achieved and these mouse models have been characterized for anatomical, neuroendocrine, and behavioral sequelae. The profile of results, consistent with current knowledge of CRF function from more traditional assays, indicates that enhancement of CRF function is associated with an activation of the hypothalamic-pituitary-adrenal axis, an anxious phenotype, alterations in cognitive performance and reductions in feeding. In general, blockade of CRF function produces the opposite effects. Genetic mouse models allow further analysis of specific elements in the CRF circuitry for which more traditional tools have not existed. These animal models are valuable for increasing our understanding of the underlying pathology associated with a variety of psychiatric and neuroendocrine disorders and for the development and testing of novel treatment agents.