SAGE (Serial Analysis of Gene Expression) analysis in the amygdala of P301L tau mutant pR5 mice identifies 29 deregulated genes that includes <i>Sfpq</i>.

<p>SAGE was used to obtain a total of 92,000 sequence tags from pooled amygdalae dissected from ten 10 month-old male pR5 mice (P301L) and ten wild-type (WT) littermate controls. Numbers of counted tags are listed for the two genotypes; ‘combined’ indicates that more than one tag was obtained per deregulated gene (for these, the individual tags are listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035678#pone-0035678-t002" target="_blank">Table 2</a>). 29 genes presented a significant (p<0.01) regulation, including nuclear and mitochondrial encoded mitochondrial genes that are shown in light grey (Gene ID for mt-Co1: 17708; mt-Co3: 17710; mt-Atp8: 17706). Of these, 11 were up- (in white) and 14 down-regulated (in grey), with mitochondrial genes indicated (in <b>bold</b>).</p

Deregulation of the nuclear factor <i>Sfpq</i> in tau transgenic mice.

<p>(A) Transcriptomic SAGE analysis of P301L tau mutant pR5 (TG) compared to wild-type (WT) amygdala identified differentially expressed genes within several functional categories (pie chart). The strongly deregulated ‘transcription’ genes (green) included <i>Sfpq</i>. (B) Scheme of the domain structure of the 707 amino acid-long nuclear protein SFPQ. The amino-terminal glutamic acid (E)/glutamine(Q)/proline(P)-rich domain is followed by two RNA/DNA-binding domains (RRMs).</p

Tau transfection causes SFPQ aggregation in postmitotic cells.

<p>(A) Mitomycin C (Mito C)-mediated cell cycle arrest or neuronal differentiation with retinoic acid (RA) of V5-tagged wild-type or P301L tau-expressing SH-SY5Y compared to untransfected (CT) SH-SY5Y neuroblastoma cells reveals SFPQ aggregates (arrows) in the cytoplasm that are not seen in CT. Insets: detailed view of vesicular SFPQ in the cytoplasm. Nuclear staining: DAPI (blue). (B) Western blotting reveals that total levels of SFPQ are not altered under any of these conditions. Actin has been used for normalisation.</p

Neuronal and glial expression of SFPQ revealed in non-transgenic wild-type (CT) control mouse brain shown for the amygdala (A) and the hippocampus (B,C).

<p>Double immunofluorescence for SFPQ (green)/MAP2 (red) (A,B) and SFPQ (green)/GFAP (red) (C) reveals an exclusively nuclear localization in both neurons and astrocytes of WT mice.</p