NEUROENDOCRINE, IMMUNE, AND BEHAVIORAL ACTIONS OF CRH

描述（改编自申请人的摘要）：促肾上腺皮质激素释放 激素（CRH）最初是一种41个氨基酸下丘脑神经肽 被确定为下丘脑-垂体-肾上腺的主要调节器 轴，通过其调节垂体ACTH的合成和释放。 CRH 其受体也广泛分布在大脑中， CRH已经被假定为介导许多行为反应， 应力 CRH也存在于外周免疫细胞中。 CRH在 大脑被认为会抑制免疫反应， 炎症，而CRH发现在周围的网站急性 据报道，炎症可增强急性炎症性 反应 研究人员建议确定行为和 CRH的免疫作用，通过研究CRH缺陷小鼠， 通过同源重组来复制CRH等位基因。 他们 已经从转基因小鼠中开发出了产生CRH的永生细胞系 CRH-T抗原构建体，并建议开发第二个转基因 使用T抗原的温度敏感突变体的小鼠品系， 免疫来源的更分化的产生CRH的细胞系。 与 这两种转基因方法，研究人员将测试 CRH参与行为和免疫反应的假说 压力

DESCRIPTION (Adapted from Applicant's Abstract): 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.