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. 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.