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.
This study investigates which IL-1R1 expressing cell type (s) mediate IL-1 induced behavior changes. We will create a genetic model in which IL-1R1 expression will be restricted to the cell type of interest to dissect the role of cell type specifi IL-1R1 mediated effects. This model will be broadly useful for numerous studies on the cellular mechanisms of IL-1 related behavior disorders.
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