Core--Biology

该项目的重点是CRF超家族肽及其结合蛋白，受体和调节剂在整合内分泌，自主神经，行为和免疫应激反应中的作用。该计划的第一个目的是表征CRF家族配体，其受体和结合蛋白之间的物理相互作用，并确定激活下游信号事件所需的基序。第二个目的是探索这些分子在细胞和系统水平上的生理和病理生理意义，并研究蛋白质表达和分泌的控制以及作用模式。解决复杂的配体/受体系统的问题是由关键科学的可用性促进的。 工具.因此，该核心应用程序旨在提供转基因小鼠、抗体和免疫测定，以进行各个项目提出的综合研究。过表达CRF系统组分的转基因小鼠或缺乏一种或多种CRFR和/或配体的空突变小鼠对于阐明这些配体和受体在正常发育和疾病状态中的生理作用是必不可少的。体外和体内基因产物的检测和/或中和依赖于对CRF超家族肽及其可溶性结合蛋白和膜结合受体具有适当特异性的高亲和力和高升抗体。还需要测量由CRF受体-配体系统调节的因子，包括垂体激素ACTH和肾上腺类固醇皮质酮。 该核心可以提供转基因小鼠，高质量的抗体和分析服务，这些服务需要训练有素的人员和专业设备，否则由于成本高，单个项目无法获得这些服务。建立一个核心可以降低成本，改善质量控制，提高效率，使技术人员专业化，使协议标准化，并使设备和空间专用化。核心B将由K.- F. Lee（转基因小鼠单位，5%努力）和W. Vale（抗体生产和检测服务，3%的工作量）。

This Program Project focuses on the role of CRF superfamily peptides and their binding proteins, receptors and modulators in the integration of endocrine, autonomic, behavioral and immune responses to stress. The first aim of this Program is to characterize physical interactions between CRF family ligands, their receptors and binding proteins and to define motifs required to activate downstream signaling events. The second aim is to explore the physiologic and pathophysiologic significance of these molecules at the cellular and system levels and to study the control of protein expression and secretion as well as modes of action. Addressing the questions of a complex ligand/receptor system is facilitated by the availability of key scientific tools. This core application is therefore designed to provide transgenic mice, antibodies, and immunoassays necessary to conduct the integrated studies proposed by the individual Projects. Transgenic mice overexpressing components of the CRF system, or null-mutant mice lacking one or more CRFRs and/or ligands, are essential for elucidating the physiologic roles of these ligands and receptors in normal development and in disease states. Detection and/or neutralization of gene products in vitro and in vivo are dependent on high affinity and high liter antibodies of appropriate specificity against CRF superfamily peptides and their soluble binding proteins and membrane bound receptors. Measurement of factors modulated by the CRF receptor-ligand system, including pituitary hormone ACTH and adrenal steroid corticosterone, are also required. This Core can provide transgenic mice, high quality antibodies and assay services that require highly trained personnel and specialized equipment which would otherwise be unavailable to individual projects due to high cost. The establishment of a Core permits reduced costs, improved quality control, efficiency, specialization of technical personnel, standardization of protocols and the dedication of equipment and space. Core B will be under the overall responsibility of Drs. K.-F. Lee (transgenic mice unit, 5% effort) and W. Vale (antibody production and assay services, 3% effort).