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. Author manuscript; available in PMC: 2016 Aug 10.
Published in final edited form as: Acta Neuropathol. 2012 Apr 25;123(6):787–805. doi: 10.1007/s00401-012-0987-3

Fig. 3. Tau phosphorylation and aggregation in mice with expression of pro- or anti-aggregant hTau40 and after switch-OFF.

Fig. 3

(a) Phosphorylated Tau species in hippocampus homogenates of pro-ON and anti-ON (16 months ON) compared to pro-ON/OFF, anti-ON/OFF (12 months ON + 4 months OFF) and controls (16 months). The most prominent phosphorylation of both hTau40 and mTau is detected in pro-ON mice using antibodies against phospho-Tau epitopes 12E8 (KXGS motifs inside the Tau repeat domain, pSer262/pSer356), PHF-1 (pSer396/pSer404), AT180 (pThr231/pSer235) and AT8 (pSer202/pThr205). Anti-ON mice show reduced Tau phosphorylation at epitopes PHF-1, AT180 and AT8 but comparable levels of 12E8 phosphorylated Tau relative to pro-ON. In pro-ON/OFF and anti-ON/OFF mice phosphorylated mTau in the range of control levels is still present. The pan-Tau antibody K9JA indicates expression of human Tau in pro-ON and anti-ON mice, β-actin serves as loading control. (b, c) Sarcosyl extraction of Tau in pro-aggregant (pro) mice with 12 months of gene expression and subsequent switch-OFF for 0.5, 1, 2 and 4 months. (a) Sarcosyl-soluble fraction. Pan-Tau staining with antibody K9JA shows a decrease and finally disappearance of soluble hTau40 over time, whereas endogenous mTau levels remain unaffected. β-actin serves as loading control. (b) Sarcosyl-insoluble fraction. At 12 months, pro-aggregant ON mice show insoluble hTau40 and mTau. Insoluble hTau40 vanishes within 0.5-1 months OFF, whereas insoluble mTau persists over a time period of 4 months OFF but tends to decrease gradually. Control (con) mice do not accumulate insoluble Tau.