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

描述（由申请人提供）：众所周知，白细胞介素-1（IL-1）在大脑中的作用导致许多行为异常，包括疾病行为、焦虑加剧、重度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。在这项探索性资助中，我们将创建一种新的遗传小鼠模型，该模型在特定的细胞类型上选择性表达IL-1 R1。在该小鼠模型中，我们可以限制IL-1 R1在其天然启动子下的细胞类型特异性表达，从而允许在仅在感兴趣的细胞类型中以生理水平表达IL-1 R1的小鼠中分析IL-1介导的作用。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-1 R1基因表达，并且通过添加到IL-1 R1蛋白的C末端的3 HA标签将促进IL-1 R1蛋白的检测。我们将使用该模型来确定细胞类型特异性IL-10的作用。 1 R1表达在免疫刺激后的疾病行为和空间学习/记忆中起作用。

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.