Striatal Projection Neurons Require Huntingtin for Synaptic Connectivity and Survival.

Journal Article (Journal Article)

Huntington's disease (HD) is caused by an autosomal dominant polyglutamine expansion mutation of Huntingtin (HTT). HD patients suffer from progressive motor, cognitive, and psychiatric impairments, along with significant degeneration of the striatal projection neurons (SPNs) of the striatum. HD is widely accepted to be caused by a toxic gain-of-function of mutant HTT. However, whether loss of HTT function, because of dominant-negative effects of the mutant protein, plays a role in HD and whether HTT is required for SPN health and function are not known. Here, we delete Htt from specific subpopulations of SPNs using the Cre-Lox system and find that SPNs require HTT for motor regulation, synaptic development, cell health, and survival during aging. Our results suggest that loss of HTT function in SPNs could play a critical role in HD pathogenesis.

Full Text

Duke Authors

Cited Authors

  • Burrus, CJ; McKinstry, SU; Kim, N; Ozlu, MI; Santoki, AV; Fang, FY; Ma, A; Karadeniz, YB; Worthington, AK; Dragatsis, I; Zeitlin, S; Yin, HH; Eroglu, C

Published Date

  • January 21, 2020

Published In

Volume / Issue

  • 30 / 3

Start / End Page

  • 642 - 657.e6

PubMed ID

  • 31968243

Pubmed Central ID

  • PMC7025500

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2019.12.069


  • eng

Conference Location

  • United States