Msh3 and Pms1 Set Neuronal CAG-repeat Migration Rate to Drive Selective Striatal and Cortical Pathogenesis in HD Mice (Updated July 15, 2024).

A recent preprint study explores the role of mismatch repair (MMR) genes in Huntington's disease (HD). The study found that knockout alleles for certain MMR genes, specifically Msh3 and Pms1, can rescue certain phenotypes associated with HD in mice. These phenotypes include somatic Htt DNA CAG-repeat expansion, transcriptionopathy, and mHtt protein aggregation. The study also reveals that Msh3 and Pms1 set the linear rate of neuronal mHtt CAG-repeat migration, which drives repeat-length dependent pathogenesis. This research provides insights into the mechanisms underlying HD and offers potential targets for HD suppression. [Extracted from the article]