Fig. 4: Hyperphosphorylation of tau in MAPTInt10+3 and MAPTS305N;Int10+3 mice.
a, Immunostaining of phosphorylated tau detected by CP13, PHF-1, AT180 and AT270 antibodies in the brains of 15-month-old WT, MAPT KI, MAPTInt10+3 KI and MAPTS305N;Int10+3 KI mice and patients with FTLD with Int10+3 and S305N mutations on the MAPT gene, respectively, with at least three biological replicates with similar observations. Scale bars, 50 µm (mouse data) and 25 µm (data from patients with FTLD). b,c, Immunoblotting of phosphorylated and total tau detected by CP13, AT8, PHF-1, K9JA, Tau13 and HT7 antibodies in the Tris-soluble fraction of brain lysates from MAPT KI, MAPTInt10+3 KI and MAPTS305N;Int10+3 KI mice at 12 months of age (n = 6 for each group, n = 3 female and n = 3 males) and in PS19 mice at 9 months of age (b) and quantification (c). d, Relative amount of phospho-tau peptides by LC–MS analysis in the brains of 10- to 18-month-old MAPT KI (n = 6; sex matched), MAPTInt10+3 KI (n = 5; n = 3 female and n = 2 males), and MAPTS305N;Int10+3 KI mice (n = 9; n = 4 females and n = 5 males). e, Summary of histological visual quantification analyses of tau phosphorylation detected by several phospho-tau antibodies. In c and d, the data represent the mean ± s.e.m. (two-way ANOVA Tukey’s multiple comparison test).
