GSE184551 Macrophages from Rosa26-integrated Cas9-expressing C57BL/6 mice have a putative TRIF-mediated defect in the TLR-3/4 signaling

Contributors : Raktima Raychowdhury ; Matteo Gentili ; Ang Cui ; Lawrence D Schweitzer ; Bo Li ; Nir HacohenSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusHere we report that the TLR4 ligand, lipopolysaccharide (LPS), and TLR3 ligand, polyinosinic:polycytidylic acid (poly (I:C)) failed to activate IRF3 or STAT1 in bone marrow derived macrophages (BMMs) isolated from two independently generated lines of Rosa26-integrated Cas9-expressing C57BL/6 (B6) mice. RNA-sequencing analysis reveals that hundreds to thousands of genes including interferon stimulated genes were differentially expressed in BMMs from these Cas9 strains compared to B6 upon LPS stimulation. Furthermore, the NF-kB signaling axis and TRIF mediated necroptosis were also strongly reduced in response to LPS and poly (I:C). In contrast there were no defects in the responses of BMMs to ligands of the RIG-I, STING, TLR2, TLR9 and IFN receptors. The TLR3 and TLR4 signaling were observed in the B6 but not 129 background, and with Cas9 integrated at the Rosa26 but not H11 locus. However, integration at the Rosa26 site, CAG promoter-driven Cas9 or eGFP were not individually sufficient to cause the defect. Taken together this study suggests a putative TRIF-mediated defect in TLR-3/4 signaling in BMMs from commercially available and widely-used C57BL/6-Cas9-expressing mice.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research