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

ABSTRACT: 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 Htt^Q111 mice, of Hdac2 or Hdac3 in medium-spiny striatal neurons that exhibit extensive CAG expansion and exquisite disease vulnerability. Both knockouts moderately attenuated CAG expansion, with Hdac2 knockout decreasing nuclear huntingtin pathology. Hdac2 knockout resulted in a substantial transcriptional response that included modification of tra

SUBMITTER: Kovalenko M 

PROVIDER: S-EPMC7581428 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature