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Publication : Dissecting adrenal and behavioral responses to stress by targeted gene inactivation in mice.

First Author  Brewer JA Year  2003
Journal  Stress Volume  6
Issue  2 Pages  121-5
PubMed ID  12775331 Mgi Jnum  J:97729
Mgi Id  MGI:3576181 Doi  10.1080/1025389031000116460
Citation  Brewer JA, et al. (2003) Dissecting adrenal and behavioral responses to stress by targeted gene inactivation in mice. Stress 6(2):121-5
abstractText  To define the molecular pathways modulating adrenal and behavioral responses to stress, we have generated mice with inactivation of hypothalamic neuropeptides and signaling pathways. Studies in mice deficient in corticotropin-releasing hormone (CRH) have revealed the essential role for CRH in adrenal glucocorticoid production in response to many physiological and psychological stressors. Immune system activation in CRH-deficient mice provides a unique exception to the necessity for CRH in stimulating adrenal glucocorticoid production. By analyzing mice deficient in interleukin-6 (IL-6) and CRH, we find that restoration of glucocorticoid output with inflammation is largely mediated by dysregulated IL-6 production. Current studies focus on identifying cellular and gene targets by which glucocorticoids regulate immune system function. In contrast to impaired adrenocortical responses to stress, CRH-deficient mice exhibit normal behavioral responses to stress. To determine signaling pathways that may contribute to the behavioral responses to stress, we have generated and analyzed mice deficient in adenylyl cyclase type 8 (AC8). AC8 deficient mice have intact adrenocortical responses to stress, but an inability to undergo stress-induced alterations in behavior.
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