Figure 1.

Gene-edited Trem2^R47H and Trem2^−/− mice are specifically modified in the TREM2 gene with no off-target effects on other TREM genes in the locus unlike the Trem2^KOMP mice. A, no detectable Trem2 mRNA in the gene-edited Trem2^−/− brains under any treatment conditions; B, Trem2 mRNA is significantly down-regulated upon LPS treatment in WT and R47H Trem2 brains; C, no detectable Trem2 mRNA in the gene-edited Trem2^KOMP brains under any treatment conditions; D and E, Trem1 is up-regulated upon LPS stimulation in gene-edited Trem2^−/− and Trem2^R47H brains, comparable with corresponding WT control brains; F, Trem1 up-regulation in the Trem2^KOMP−/− mice post-stimulation is lower compared with the in-house mice and age-matched littermate WT controls; G and H, no significant changes were noted in Treml1 levels in WT, gene-edited Trem2^−/−, and Trem2^R47H brain samples with saline treatment and LPS stimulations; I, Treml1 is highly up-regulated in the Trem2^KOMP−/− mice under basal conditions (saline treatment) and remains high upon LPS treatment; J and K, Treml2 is up-regulated 2–4-fold upon LPS treatment in the in-house Trem2^−/− mice and the Trem2^R47H mice; L, Treml2 mRNA is significantly reduced in the Trem2^KOMP mice under both basal and LPS-stimulated conditions. All results are presented as -fold change over saline-treated WT controls. *, p < 0.05; **, p < 0.01; ***, p < 0.001; ****, p < 0.0001; data represented as mean ± S.D.; statistical analysis: one-way ANOVA with Sidak's correction for multiple comparison.