Interleukin 1 Type 1 Receptor Restore: A Genetic Mouse Model for Studying Interleukin 1 Receptor-Mediated Effects in Specific Cell Types

• DOI: 10.1523/jneurosci.3199-14.2015
• Publication Date: 2015-02-27T01:22:12Z
• Authors: Xiaoyu Liu; Tetsuji Yamashita; Qun Chen; Natalya Belevych; Daniel B. Mckim; Andrew J. Tarr; Vincenzo Coppola; Nikitaa Nath; Daniel P. Nemeth; Zunera W. Syed; John F. Sheridan; Jonathan P. Godbout; Jian Zuo; Ning Quan
• Keywords: Interleukin-1 receptor

Interleukin-1 (IL-1) mediates diverse neurophysiological and neuropathological effects in the CNS through type I IL-1 receptor (IL-1R1). However, identification of IL-1R1-expressing cell types cell-type-specific functions IL-1R1 remains challenging. In this study, we created a novel genetic mouse model which gene expression is disrupted by an intronic insertion loxP flanked disruptive sequence that can be deleted Cre recombinase, resulting restored under its endogenous promoters. A second mutation was introduced at stop codon to allow tracking protein 3HA tag mRNA tdTomato fluorescence. These animals were designated as r/r exhibited knock-out phenotype. We used globally mice (IL-1R1 GR/GR ) reporter observed concordant labeling brain endothelial cells. Two restore lines generated: Tie2Cre-IL-1R1 LysMCre-IL-1R1 . Brain COX-2 expression, leukocyte infiltration, global microglia activation induced intracerebroventricular injection IL-1β not or mice, but mice. results reveal cells alone sufficient mediate these central IL-1-induced responses. addition, ex vivo stimulation increased bone marrow wild-type, , demonstrate valuable tool for studying IL-1R1.