Corticotropin releasing hormone (CRH) is a 41 amino acid hypothalamic neuropeptide initially identified as a major regulator of the hypothalamic-pituitary-adrenal axis, via its regulation of pituitary ACTH synthesis and release. CRH and its receptor are also found widely distributed in the brain, where CRH has been postulated to mediate many of the behavioral responses to stress. CRH is also found in peripheral immune cells. CRH within the brain is thought to cause suppression of the immune response to inflammation, whereas CRH found in the periphery at sites of acute inflammation has been reported to enhance the acute inflammatory response. The investigators propose to determine the behavioral and immune actions of CRH by studying a CRH-deficient mouse that they have created by homologous recombination to inactivate both CRH alleles. They have developed immortalized CRH-producing cell lines from mice transgenic for CRH-T antigen constructs, and propose to develop a second transgenic mouse strain using a temperature-sensitive mutant of T antigen to create more differentiated CRH-producing cell lines of immune origin. With both of these transgenic approaches, the investigators will test the hypothesis that CRH is involved in the behavioral and immune responses to stress.
