Generation of the striatal specific mouse model of HD. (A) Schematics illustrate the strategy to use cell-type-specific Cre to selectively activate mhtt-exon1 expression in all neurons in the brain (pan-neuronal model), only in CPNs (cortical model; ), and only in striatal MSNs and a subset of interneurons (asterisks) in the cortex (striatal model). (B) Immunohistochemical staining using polyclonal EM48 antibody, which is specific to aggregated forms of mhtt , reveals a cell-autonomous accumulation of nuclear mhtt aggregates in the striatum of the striatal model at 6 months of age. Inset in B shows at a higher magnification the EM48 staining in the nucleus is consisted of diffuse nuclear staining, and not large nuclear inclusions or smaller microaggregates. (C) EM48 staining reveal strong nuclear staining in the striatum (str) but sparse nuclear staining in the cortex (cor), inset in C shows diffuse EM48 nuclear staining of one cell at high magnification. cc: corpus callosum. Finally, there is no nuclear EM48 staining in other brain regions including cerebellum (D) and brain stem (E). Scale bars are 50 μm except in B (200 μm) and insets in B and C (10 μm).