Figure 1. CUG^exp–positive ribonuclear inclusions and co-localization with MBNL1 in SCA8 cerebellum.

(A) CUG-positive nuclear foci (RED) in SCA8 mouse and human cerebellum. CUG ribonuclear inclusions detected by FISH (RED) in SCA8 (human and mouse) and DM1 (human) Purkinje cells (PCs), molecular layer (ML) interneurons (human and mouse), and deep cerebellar nuclei (DCN) (mouse) showing CUG positive nuclear foci (RED) in human SCA8 and DM1 cerebellum (top) and in SCA8 BAC-EXP1 mice (bottom). (B) FISH and IF analysis of CUG foci and MBNL1 in human cerebellar autopsy tissue. CUG foci co-localize with MBNL1 in molecular layer interneurons (ML) (SCA8) (top row; arrowheads) but not in Purkinje cells (PC) (SCA8 or DM1) (middle and bottom rows, arrows). Co-localization is indicated by a yellowish color when the red CUG foci, green MBNL1 and blue DAPI overlap in the nucleus. (C) CUG foci co-localize with Mbnl1 in ML interneurons and deep cerebellar nuclei (DCN) in SCA8 BAC-EXP mice (arrowheads, top and bottom rows). Images are representative examples of staining with all 3 channels acquired at equal intensities in sequential order on a confocal microscope, merged along the Z-axis, digitally zoomed, cropped, and adjusted for brightness and contrast for publication.