TFEB-vacuolar ATPase signaling regulates lysosomal activity and immune response in tauopathy

Transcription factor EB (TFEB) mediates gene expression through binding to the Coordinated Lysosome Expression And Regulation (CLEAR) sequence. We created a knock-in mouse line in which the CLEAR sequence of ATP6V1H was mutated. Crossing the CLEAR mutant with PS19 mice led to higher tau pathology but dampened glial cell activation. snRNA-seq revealed that the CLEAR mutant failed to be activated in tauopathy conditions. Overall design: single nuclear RNA sequencing (snRNA-seq) of hippocampus of wild-type and PS19 tau transgenic mice and CLEAR mutant and CLEAR mutant crossing with PS19 mice at 9 month-of-age; and bulkRNAseq in WT and PS19 with 4 or 9 months old.