Fig. 1

Predominant hTau expression in the hippocampus of dox-administered hTau368 mice. a Strategy to express hTau1-368 fragment (hTau368) in transgenic mice. The hTau368 expression was controlled by a tet-on system in combination with the neuronal specific Eno2 promoter. In the presence of doxycycline (dox-on), reverse tetracycline transactivator (rtTA) binds to the tetracycline-responsive element (TRE) to initiate hTau368 expression. In the absence of doxycycline (dox-off), hTau368 expression stops, as rtTA cannot bind to TRE. b–d Relatively prominent immunofluorescent intensity of hTau368 in the hippocampus following 2-month dox treatment. Representative sagittal (b) and coronal (c) images are shown. One-way ANOVA followed by Tukey's multiple comparisons tests, *** P < 0.001, n = 4 sections from 4 mice. Data were normalized to the mean value in the hippocampus. e, f Western blotting showed relatively prominent human tau expression in the hippocampus of dox-treated hemizygous hTau368 mice. One-way ANOVA followed by Tukey’s multiple comparisons tests, *** P < 0.001, compared with the hippocampus; n = 3 mice in each group. g, h hTau368 distribution in both neuronal soma and neurites in multiple hippocampal subregions. One-way ANOVA followed by Tukey's multiple comparisons tests, *P < 0.05, compared with CA2; n = 4 sections from 4 mice. Data were normalized to the mean value in CA2. i, j hTau368 mice (hemizygous) showed time-dependent increase of hTau expression in the hippocampus following dox administration. One-way ANOVA followed by Tukey's multiple comparisons tests, *P < 0.05, ***P < 0.001; n = 3 mice in each group, sacrificed at 15–16 months old. Data were normalized to the mean value of the 1-month Dox-treatment group. k, l The hTau level in the hippocampus of hTau368 mice (hemizygous) gradually decreased during 1–3 months after dox retraction (dox-off). n = 4 mice in each group