(A) Sections of the cortex and dentate gyrus (DG) from 11-week-old age-matched control, R6/2, R6/2•Irs2ntg, and R6/2•Irs2+/–•Irs2βtg mice immunostained with GFAP antibody. Scale bars: 100 μm (cortex); 20 μm (cortex, insets); 50 μm (DG). (B) GFAP signal, quantified from A. (C) Cortex from 6- and 11-week-old R6/2, R6/2•Irs2ntg, and R6/2•Irs2+/–•Irs2βtg mice stained with anti-Htt antibody (red). Nuclei are stained with DAPI (blue). Representative images of cortical neurons are shown. Scale bars: 50 μm. (D–G) Quantification of inclusion body frequency (D and E) and size (F and G) in cortex (D and F) and striatum (E and G). (H) Western blots of brain extracts prepared from 11-week-old control, R6/2, R6/2•Irs2ntg, and R6/2•Irs2+/–•Irs2βtg mice solubilized in Triton or SDS, resolved by SDS-PAGE, and probed with Htt antibody. Tubulin was used for normalization. (I) SDS-insoluble Htt from H, normalized to tubulin and expressed as a percentage of R6/2 (n = 4). *P < 0.05; **P < 0.01.