Figure 4.
Generation of an in vivo model of 82Q striatal aggregation and toxicity. Wistar rats were transduced in the striatum with 18Q or 82Q expressing LV by sterotaxic injection and examined 8, 10, or 12 weeks after transduction (n = 6). (a) Representative coronal sections of the striatum demonstrating GFP expression, DARPP-32 depletion and 2B4 stained huntingtin aggregates from a GFP.82Q LV–injected rat (4× tiled images). (b–e) Evaluation of the neurotoxicity of 18Q (10 weeks) and 82Q (8, 10, and 12 weeks) on DARPP-32 stained striatal sections. As expected, no striatal degeneration was observed in the 18Q-transduced striatum. Most significant striatal degeneration was observed at the 10-week time point in the 82Q-transduced striatum. (f–i) No Htt inclusions were detected in the 18Q-transduced striatum with 2B4 antibody. The highest level of huntingtin inclusions were detected in the 82Q-transduced striatum at the 10-week time point. Scale bars represent 100 µm (j–m) DAPI, c-Myc (MYC) and ubiquitin triple staining indicates that huntingtin inclusions (c-Myc tagged) are ubiquitinated. Scale bar represents 25 µm. (n–q) DAPI, 2B4 and GFP triple staining indicates the presence of nuclear Htt inclusions within 82Q-transduced neurons. Scale bar represents 25 µm.