Physiological Roles of Receptor-Associated Immunophilins

受体相关亲免素的生理作用

• 批准号: 6835062
• 负责人: Marc B Cox
• 金额: $ 4.4万
• 依托单位: MAYO CLINIC ARIZONA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6835062
• 关键词: corticosteroid receptors; cortisol; genetically modified animals; hypercortisolism; laboratory mouse; liver cells; peptidylprolyl isomerase; postdoctoral investigator; protein structure function; receptor binding; receptor expression

DESCRIPTION (provided by applicant): The goals of this project are to understand roles of the steroid hormone receptor-associated immunophilins (FKBP51 and FKBP52) in glucocorticoid receptor (GR)-mediated physiological processes, and to assess the likelihood that the FKBP51 and FKBP52 null mice could serve as model systems for the study of known human diseases associated with altered glucocorticoid responses. First, the FKBP51 and FKBP52 gene expression patterns will be assessed in mice using various histochemical and immunohistochemical staining methods. Next, an altered GR response in mice lacking the FKBP51 and/or FKBP52 genes will be demonstrated as assessed by GR ligand binding and GR-mediated gene expression in hepatocytes isolated from FKBP51 and FKBP52 null mice. Finally, various physiological parameters that are typically altered in response to hypo- and/or hypercortisolism (e.g. truncal obesity) will be assessed in FKBP51 and FKBP52 null mice. FKBP51 overexpression has been attributed to cortisol resistance in squirrel monkeys. Thus, these studies could also contribute drugs to a better understanding of the mechanism by which patients acquire resistance to corticosteroid drugs.

描述（由申请人提供）：该项目的目标是了解类固醇激素受体相关的亲免蛋白（FKBP51 和 FKBP52）在糖皮质激素受体（GR）介导的生理过程中的作用，并评估 FKBP51 和 FKBP52无效小鼠可以作为研究与糖皮质激素反应改变相关的已知人类疾病的模型系统。首先，将使用各种组织化学和免疫组织化学染色方法评估小鼠中的 FKBP51 和 FKBP52 基因表达模式。接下来，通过从 FKBP51 和 FKBP52 缺失小鼠分离的肝细胞中的 GR 配体结合和 GR 介导的基因表达来评估，将证明缺乏 FKBP51 和/或 FKBP52 基因的小鼠中 GR 反应的改变。最后，将在 FKBP51 和 FKBP52 缺失小鼠中评估通常因皮质醇功能低下和/或皮质醇增多症（例如躯干肥胖）而改变的各种生理参数。 FKBP51 过度表达归因于松鼠猴的皮质醇抵抗。因此，这些研究还可以有助于更好地理解患者对皮质类固醇药物产生耐药性的机制。