Mutant Huntingtin Causes Context-Dependent Neurodegeneration in Mice with Huntington's Disease

• DOI: 10.1523/jneurosci.23-06-02193.2003
• Publication Date: 2018-04-12T23:25:04Z
• Authors: Zhao-Xue Yu; Shi-Hua Li; Joy Evans; Ajay Pillarisetti; He Li; Xiao-Jiang Li
• Keywords: Polyglutamine tract; Huntingtin Protein

Huntington's disease (HD) mouse models that express N-terminal huntingtin fragments show rapid progression and have been used for developing therapeutics. However, light microscopy reveals no significant neurodegeneration in these mice. It remains unclear how mutant induces neurodegeneration. Using caspase staining, terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling, electron microscopy, we observed N171-82Q mice, which the first 171 aa of huntingtin, displayed more degenerated neurons than did other HD models. The was also evidenced by increased immunostaining glial fibrillary acidic protein ultrastructural features apoptosis. R6/2 exon 1 showed dark, nonapoptotic mitochondria associated with huntingtin. In repeat knock-in mice (HdhCAG150), full-length cytoplasmic organelles were found both axons neuronal cell bodies association not labeled an antibody to amino acids 342-456. Transfection cultured cells revealed fragment (amino 1-208 plus a 120 glutamine repeat) caused greater increase activity longer fragments. These results suggest context-dependent may be mediated different addition, this study has identified neurodegenerative markers evaluation therapeutic treatments