Animals
All protocols were approved by Yale Institutional Animal Care and Use Committee (IACUC) (2023-07281).
Human P301S tau transgenic (PS19) mice with B6C3F1 background34 were obtained from the Jackson Laboratory. The mice express mutant human MAPT gene, which results in a five-fold greater amount of human mutant tau protein (P301S 1N4R tau) than endogenous mouse tau. Grn−/− mice with C57BL/6 J background35 were obtained from the RIKEN Bioresource Center. To generate 6 genotypes used in this study (WT, Grn+/−, Grn−/−, PS19, PS19 Grn+/−, and PS19 Grn−/−) with minimal differences in genetic background, PS19 and Grn−/− mice were first crossed to generate PS19 Grn+/− and Grn+/− mice and then these mice were crossed. The resulting littermates with WT, Grn+/−, Grn−/−, PS19, PS19 Grn+/−, and PS19 Grn−/− genotypes born with the ratio 1:2:1:1:2:1 were…
