Fig. 1

Generation of htau-KI mice. a Development strategy for the htau-KI mouse line. The human tau gene (exon 2–12, orange rectangles) was placed into the murine tau locus (green rectangles) by homologous recombination. The gene Saitohin (STH) is present in the human tau gene and was also included in the targeting vector. SHA = short homology arm, LHA = long homology arm, HR = homologous recombination, Flp = Flippase, F3 = Flp recombination target site, FRT = Flp recombination target site, NeoR = neomycin resistance gene, PuroR = puromycin resistance gene. b Mouse (anti-tau clone T49) and human (anti-tau13) tau-specific antibodies confirmed the absence of murine tau and the presence of human tau in dephosphorylated brain extracts of htau-KI mice, respectively. Faintly visible bands of human tau in WT mice are due to incomplete stripping of the membrane. M = male, F = female at ages of 6 and 12 months. The images have been cropped. Original files can be found as Additional files 4, 5 and 6. c Differential expression of 770 AD-related genes in frontal cortex of 13-month-old WT mice (n=6) vs. htau-KI (n=6) mice analyzed by nCounter Mouse AD gene expression panel. Depicted is a volcano plot showing log2(fold change) in dependence of −log10 of P-values. Red circle marks the only differentially expressed AD-related gene, MAPT. d Representative PCR using murine- and human tau-specific primers confirming the loss of the mouse tau gene and the presence of the human tau gene in homozygous htau-KI mice. Murine tau PCR product: 280 bp, human tau PCR product: 399 bp. Original image file can be found as Additional files 7. e A pan-specific tau antibody (Tau-5) on Western blot showed equal expression levels of tau in htau-KI mice compared to WT mice. M = male, F = female at ages of 6 and 12 months. Uncropped image files can be found as Additional files 8, 9, 10 and 11. f Quantification of total tau expression from e in WT and htau-KI mice with GAPDH as reference protein. Mean ± SD. n=4