NEUROENDOCRINE, IMMUNE, AND BEHAVIORAL ACTIONS OF CRH

描述(摘自申请者摘要)：促肾上腺皮质激素释放 激素(CRH)最初是由41个氨基酸组成的下丘脑神经肽。 被认为是下丘脑-垂体-肾上腺的主要调节因子 轴，通过其调节垂体ACTH的合成和释放。CRH 和它的受体也广泛分布在大脑中， CRH被认为是许多行为反应的中介。 压力。CRH也存在于外周免疫细胞中。中的CRH 大脑被认为会导致免疫反应被抑制 炎症，而CRH在急性炎症部位周围可见。 据报道，炎症可以增强急性炎症。 回应。调查人员建议确定行为和行为 CRH对CRH缺陷小鼠免疫作用的研究 通过同源重组来灭活两个CRH等位基因。他们 已经从转基因小鼠中培育出永生化的CRH产生细胞系 对于CRH-T抗原的构建，并建议开发第二种转基因 小鼠品系使用温度敏感的T抗原突变体创建 更多分化的产生CRH的免疫来源的细胞系。使用 这两种转基因方法，调查人员将测试 CRH参与行为和免疫反应的假说 来施加压力。

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.