Fig. 7. HspBP1 expression accounts for the nuclear accumulation of mutant HTT in KI mouse striatum.

a mEM48 western blot analysis of the cortex and striatum of HD140Q KI mice at different ages revealing that mutant exon 1 HTT is constantly expressed but selectively forms aggregates in the aged striatum. More than three times of experiments were performed independently. b Western blotting of wild-type mouse brains showing that HspBP1 is more abundant in the striatum and its expression increases with age. c Western blotting of cultured mouse striatal neurons showing that targeting HspBP1 by AAV Cas9/HspBP1-gRNA could effectively reduce HspBP1 expression. d Injection of AAV control gRNA and AAV HspBP1-gRNA into the striatum of KI/Cas9 mice at 25 weeks of age. The mouse brain image was remixed from the clipart https://commons.wikimedia.org/wiki/File:Mouse_Dorsal_Striatum.pdf, under the Creative Commons Attribution-Share Alike International license. e Eight weeks after injection, mEM48 immunostaining of the injected striatum showing that deletion of HspBP1 could markedly reduce the nuclear accumulation of mutant HTT. Scale bar: 40 μm. f Quantitative analysis of nuclear HTT staining in the AAV-injected mouse striatum. The data were obtained from five images in the striatum per mice (n = 3 mice per group, ****P < 0.0001, one-way ANOVA followed by Tukey’s multiple comparison tests, F = 82.84, p < 0.0001). Data are presented as mean values ± SEM. Source data are provided as a Source Data file.