Generation of humanized TREM2 and hTREM2‐R47H mouse lines and their effects on disease pathogenesis in 5xFAD mice

Microglial reactivity to amyloid plaques was less in hTREM2 knock-in line compared to mTrem2, suggesting that hTREM2 itself is not fully functional in the murine biologic system. Nevertheless, compared to mTrem2 and hTREM2, hTREM2-R47H microglia do not down-regulate their homeostatic genes in response to amyloid-beta. Further, the magnitude of the effect of R47H in hTREM2 appears stronger than R47H in mTREM2, suggesting that humanization of disease relevant genes offers additional insights into disease mechanisms.