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Chunk #7 — Materials and methods — Mouse experiments

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Pathological tau drives ectopic nuclear speckle scaffold protein SRRM2 accumulation in neuron cytoplasm in Alzheimer's disease.
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All mouse experiments were reviewed and approved by the VA Puget Sound Health Care System Institutional Animal Care and Use Committee (IACUC) and conducted in an American Association for Accreditation of Laboratory Animal Care (AAALAC)-accredited animal research facility. The PS19 tau transgenic mouse model expressing human P301S mutant human tau was used in this study. This mouse model is well characterized and has a highly progressive tauopathy related phenotype. In addition, a milder mouse model of tauopathy driven by wild type human tau expression (Tau4Rtg2652) was also examined. This mouse line exhibits early-stage tau pathology, including phosphorylated tau, but not neurofibrillary degeneration [23]. PS19 mice (15 three month, 7 at seven months of age and 16 at nine months of age), Tau4Rtg2652 mice (8 at 4 months of age) and WT mice (5 at nine months of age) were anesthetized and fixed by transcardial perfusion with 4% paraformaldehyde. Brains were removed and paraffin embedded for sectioning. Coronal sections (9 microns) were prepared and stored at 4 °C until use.