IL-1R1-restore: dissecting cellular mechanisms of IL-1-mediated behavior effects

IL-1R1-restore：剖析 IL-1 介导的行为效应的细胞机制

• 批准号: 8428218
• 负责人: Ning Quan
• 金额: $ 22.94万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-12-15 至 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8428218
• 关键词: Address; Affect; Animal Model; Anxiety; Astrocytes; Behavior; Behavioral; Brain; Cells; Detection; Endothelial Cells; Fluorescence; Gene Expression; Genetic; Genetic Models; Grant; Hippocampus (Brain); Hypothalamic structure; Immune; Impairment; Interleukin-1; Interleukin-1 Receptors; Learning; Lifestyle-related condition; Literature; MAPK14 gene; Major Depressive Disorder; Maps; Mediating; Memory; Messenger RNA; Methods; Microglia; Modeling; Monitor; Mus; NF-kappa B; Neuroglia; Neurons; Pattern; Physiological; Play; Proteins; Reporting; Role; Sick Role; Signal Pathway; Signal Transduction; behavior change; brain cell; cell type; interest; mouse model; neural circuit; novel; promoter; public health relevance; selective expression

DESCRIPTION (provided by applicant): It is well known actions of interleukin-1 (IL-1) in the brain contributes to numerous behavior abnormalities, including illness behavior, heightened anxiety, major depression, and impairment in learning and memory. However, cellular mechanisms by which IL-1 affects neurons involved in these behaviors are unclear. In this exploratory grant, we will create a novel genetic mouse model that selectively expresses IL-1R1 on a defined cell type. In this mouse model, we can restrict cell type specific expression of IL-1R1 under its native promoters, thus permitting analysis of IL-1-mediated effects in mice which express IL-1R1 at physiological levels only in the cell type(s) of interest. Additional advantages of this model are IL-1R1 gene expression at mRNA level is able to be monitored by a knockin red fluorescence and detection of IL-1R1 protein will be facilitated by a 3HA tag added to the C-terminus of the IL-1R1 protein. We will use this model to determine the role cell type-specific IL- 1R1 expression plays in both illness behavior and spatial learning/memory following immune stimulation.

描述（由申请人提供）：众所周知，白细胞介素-1 (IL-1) 在大脑中的作用会导致许多行为异常，包括疾病行为、高度焦虑、严重抑郁以及学习和记忆障碍。然而，IL-1 影响参与这些行为的神经元的细胞机制尚不清楚。在这笔探索性资助中，我们将创建一种新型遗传小鼠模型，该模型可在特定细胞类型上选择性表达 IL-1R1。在该小鼠模型中，我们可以限制 IL-1R1 在其天然启动子下的细胞类型特异性表达，从而允许分析仅在以下细胞类型中以生理水平表达 IL-1R1 的小鼠中 IL-1 介导的效应。兴趣。该模型的其他优点是能够通过敲入红色荧光监测 mRNA 水平的 IL-1R1 基因表达，并且添加到 IL-1R1 蛋白 C 末端的 3HA 标签将有助于检测 IL-1R1 蛋白。我们将使用该模型来确定细胞类型特异性 IL-的作用 1R1 表达在免疫刺激后的疾病行为和空间学习/记忆中发挥作用。