Because pSRRM2 mis-localization occurs in the same brain regions as neurofibrillary degeneration, we hypothesized that pathological tau deposition provokes ectopic pSRRM2 accumulation in the neuronal soma. To test this idea, we examined the pattern of pSRRM2 staining in the brains of PS19 tau transgenic mice. This well characterized mouse model of tauopathy exhibits high level expression of the FTLD P301S mutant human tau in degenerating neurons [23]. While SRRM2 is well conserved between humans and mice [29], phosphorylation of SRRM2 is complex with potential variation between mice and humans [22, 26]. In aged PS19 mice following onset of neurofibrillary tangle deposition, pSRRM2 mis-localization becomes evident and is similar to the aberrant cytoplasmic accumulation we observed in AD brain (Fig. 2a–f, h). In non-Tg mice, mAb clone SC-35 does not detect any pSRRM2 protein (Fig. 2 g) and in 3-month-old PS19 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
