Huntingtin CAG-expansion mutation results in a dominant negative effect.

ABSTRACT: Introduction: Huntington's disease (HD) remains an incurable and fatal neurodegenerative disease long after CAG-expansion mutation in the huntingtin gene (HTT) was identified as the cause. The underlying pathological mechanism, whether HTT loss of function or gain of toxicity results from mutation, remains a matter of debate. Methods: In this study, we genetically modulated wild-type or mutant HTT expression levels in isogenic human embryonic stem cells to systematically investigate their contribution to HD-specific phenotypes. Results: Using highly reproducible and quantifiable in vitro micropattern-based assays, we observed comparable phenotypes with HD mutation and HTT depletion. However, halving endogenous wild-type HTT lev

SUBMITTER: Laundos TL 

PROVIDER: S-EPMC10505792 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature