Fig. 1
Characterization of microglia-specific PS19-TREM2 inducible mouse models
(A) Schematic illustrative of the inducible expression of TREM2-WT or TREM2-R47H knock-in alleles. The TREM2 floxed mice were bred with the Cx3cr1CreER mice to generate TREM2-WT (TREM2-WT+/+; Cx3cr1CreER/+) or TREM2-R47H (TREM2-R47H+/+; Cx3cr1CreER/+) mice. Administration of tamoxifen to these mice led to the removal of the loxP-flanked Neor gene and expression of human TREM2-WT or TREM2-R47H in microglia. (B) Illustration of induction paradigms for the expression of human TREM2-WT or TREM2-R47H in the PS19 background. (C-H) The mRNA levels of human TREM2 (C and D), mouse Trem2 (E and F), and total TREM2 (human + mouse; G and H) in the brain were quantified by qPCR. n = 10 mice/group (mixed sexes). In C–H, each datapoint (circle) represents an individual animal, male and female mice are labeled as solid and open circles, respectively. Two-tailed unpaired Student’s t tests with Bonferroni correction were used for statistical analysis. P values < 0.05 were considered to be statistically significant. ***, P < 0.001; ****, P < 0.0001; N.S., not significant. Data are mean ± SEM. (I-K) The protein levels of human TREM2 in the cortical RIPA lysate were quantified by western blot. n = 19–23 mice/group (mixed sexes). In J-K, each datapoint (circle) represents an individual animal, male and female mice are labeled as solid and open circles, respectively. Mann − Whitney tests followed by Bonferroni correction for multiple comparisons were used for statistical analysis. P values < 0.05 were considered to be statistically significant. ****, P < 0.0001; N.S., not significant. Data are mean ± SEM. (L) Representative images of the GFP, human TREM2, and IBA1 co-staining. Scale bar, 50 μm.