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Fig. 1 | Molecular Neurodegeneration

Fig. 1

From: The Trem2 R47H Alzheimer’s risk variant impairs splicing and reduces Trem2 mRNA and protein in mice but not in humans

Fig. 1

Trem2 mRNA and protein are reduced in a novel Trem2 R47H knock-in mouse model. a and b Evolutionary conservation of TREM2 at the DNA (a) and protein (b) level. c Strategy to generate Trem2 R47H knock-in (R47H ki) mice indicating the protospacer region (green), protospacer adjacent region (PAM, purple), and the introduced nucleotide changes (orange or red). The restriction site for SalI is underlined. d Trem2 and Tyrobp mRNA levels in brains from R47H ki mice. TaqMan probes for the exon 4/5 boundary were used to detect total Trem2 mRNA. TaqMan probes for the Trem2 exon 3/4 boundary were used for isoform discrimination. (N = 3, +/-SEM, one way ANOVA, Bonferroni-corrected pair-wise post hoc tests, total Trem2 WT vs. Het p = 0.0002, WT vs. Hom p < 0.0001; Trem2 isoform 1 WT vs. Het p = 0.0029, WT vs. Hom p < 0.0001; Trem2 isoform 2 WT vs. Het p = 0.0031, WT vs. Hom p = 0.0002. n.s. Non-significant). e Allele specific Trem2 mRNA expression in heterozygous R47H ki mice. Customized probes were against Trem2 R47H and its neighbor region (see also Methods). (N = 3, +/-SEM, unpaired t test, p < 0.0001). f Trem2 protein expression in microglia isolated from Trem2 wt or R47H ki mice. (N = 3,+/-SEM, one way ANOVA, p < 0.0001, Bonferroni-corrected pair-wise post hoc tests, WT vs. Het p = 0.0005, WT vs. Hom p < 0.0001). g Trem2 and Tyrobp mRNA levels in bone marrow derived macrophages (BMDM) isolated from Trem2 wt and R47H ki mice. (N = 3, +/-SEM, one way ANOVA, Bonferroni-corrected pair-wise post hoc tests, Trem2 WT vs. Het p = 0.0002, WT vs. Hom p < 0.0001; Trem2 isoform 1 WT vs. Het p < 0.0001, WT vs. Hom p < 0.0001; Trem2 isoform 2 WT vs. Het p = 0.0008, WT vs. Hom p < 0.0001. n.s. Non-significant.) h Expression levels of membrane bound and soluble Trem2 (sTrem2) protein in BMDM isolated from Trem2 wt or R47H ki mice. (N = 3, +/-SEM, one way ANOVA, Trem2 p = 0.0003, Bonferroni-corrected pair-wise post hoc tests, WT vs. Het p = 0.0026, WT vs. Hom p = 0.0002, sTrem2 p = 0.0007, WT vs. Het p = 0.0469, WT vs. Hom p = 0.0005)

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