Histone deacetylase knockouts modify transcription, CAG instability and nuclear pathology in Huntington disease mice.

Somatic expansion of the Huntington's disease (HD) CAG repeat drives the rate of a pathogenic process ultimately resulting in neuronal cell death. Although mechanisms of toxicity are poorly delineated, transcriptional dysregulation is a likely contributor. To identify modifiers that act at the level of CAG expansion and/or downstream pathogenic processes, we tested the impact of genetic knockout, in mice, of or in medium-spiny striatal neurons that exhibit extensive CAG expansion and exquisite disease vulnerability.