Interleukin 1 type 1 receptor restore: A genetic mouse model for studying interleukin 1 receptor-mediated effects in specific cell types

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

Research output: Contribution to journalArticlepeer-review


Interleukin-1 (IL-1) mediates diverse neurophysiological and neuropathological effects in the CNS through type IIL-1 receptor (IL-1R1). However, identification of IL-1R1-expressing cell types and cell-type-specific functions of IL-1R1 remains challenging. In this study, we created a novel genetic mouse model in which IL-1R1 gene expression is disrupted by an intronic insertion of a loxP flanked disruptive sequence that can be deleted by Cre recombinase, resulting in restored IL-1R1 gene expression under its endogenous promoters. A second mutation was introduced at stop codon of the IL-1R1 gene to allow tracking of the restored IL-1R1 protein by a 3HA tag and IL-1R1 mRNA by tdTomato fluorescence. These animals were designated as IL-1R1r/r and exhibited an IL-1R1 knock-out phenotype. We used IL-1R1 globally restored mice (IL-1R1 GR/GR) as an IL-1R1 reporter and observed concordant labeling of IL-1R1 mRNA and protein in brain endothelial cells. Two cell-type-specific IL-1R1 restore lines were generated: Tie2Cre-IL-1R1r/r and LysMCre-IL-1R1r/r. Brain endothelial COX-2 expression, CNS leukocyte infiltration, and global microglia activation induced by intracerebroventricular injection of IL-1 ¡5 were not observed in IL-1R1 r/rorLysMCre-IL-1R1r/r mice, but were restored in Tie2Cre-IL-1R1r/r mice. These results reveal IL-1R1 expression in endothelial cells alone is sufficient to mediate these central IL-1-induced responses. In addition, ex vivo IL-1β stimulation increased IL-1β expression in bone marrow cells in wild-type, Tie2Cre-IL-1R1r/r, and LysMCre-IL-1R1r/r, but not IL-1R1r/r mice. These results demonstrate this IL-1R1 restore model is a valuable tool for studying cell-type-specific functions of IL-1R1.

Original languageEnglish (US)
Pages (from-to)2860-2870
Number of pages11
JournalJournal of Neuroscience
Issue number7
StatePublished - Feb 18 2015
Externally publishedYes


  • Blood-brain barrier
  • Endothelial cells
  • Interleukin 1
  • Knock-in
  • Neuroinflammation
  • Restore

ASJC Scopus subject areas

  • Neuroscience(all)


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