Time-dependent alteration of gene expression after induced knockout of Trex1 in bone marrow derived macrophages.

Defects in three prime repair exonuclease (TREX1) cause the type I interferonopathy Aicardi Goutières syndrome. In absence of TREX1 some unknown DNA is accumulating in the cytosol which triggers cGAS/STING activation and type I interferon production. This analysis was designed to understand the kinetics of accumulation of the pathogenic cGAS ligand and the resulting altered gene expression upon induced loss of TREX1. Overall design: Trex1 ko was induced in bone marrow derived macrophages from Trex1FL/FL Cre-ERT2WT/KI mice and Trex1WT/FL controls by 4-Hydroxytamoxifen treatment. Cells were harvested from day 1 to day 4 after 4-OHT treatment. Total RNA was isolated using NucleoSpin RNA Kit (Macherey-Nagel). RNA was sequenced on Illumina NovaSeq 6000.