mice pSRRM2 appears as diffuse mild immunoreactivity in the cytoplasm (Fig. 2a) and there are no tangles (Fig. 2b). We find robust accumulation of cytoplasmically mis-localized pSRRM2 (Fig. 2c) in a subset of neurons and detect sparse NFTs in 7-month-old PS19 mice (Fig. 2d). By nine months of age, PS19 mice exhibit significant pSRRM2 cytoplasmic accumulation in a substantial fraction of neurons in these same regions (Fig. 2e) and have accumulated substantial hippocampal and cortical NFTs (Fig. 2f) and begun to exhibit frank neurodegeneration. To validate these findings in a mouse model of tauopathy driven by wild type human tau expression, we examined pSRRM2 accumulation in the Tau4Rtg2652 mouse line, a model with early stage tau pathology, including phosphorylated tau, but without neurofibrillary degeneration. The Tau4Rtg2652 mice exhibit a milder but disrupted nuclear speckle staining pattern for pSRRM2 (Additional file 1: Fig S1). Because expression of the tau transgene drives the primary insult in tau transgenic mice, these findings suggest that pSRRM2 mis-localization to the cytoplasm occurs in neurons as a result of pathological tau accumulation leading to neurodegeneration accompanied by mis-localization of pSRRM2. Further, these data suggest a hypothesis where cytoplasmic pSRRM2 marks a new subtype of neuropathological lesion
