Vanessa C. Wheeler

TL;DR: These phenotypes indicate a disruption of striatal cell homeostasis by the mutant protein, via a mechanism that is separate from its normal activity, and support specific stress pathways, including elevated p53, endoplasmic reticulum stress response and hypoxia, as potential players in HD.

TL;DR: In precise genetic models of juvenile HD, long polyglutamine segments change huntingtin's physical properties, producing HD-like in vivo correlates in the striatum, including nuclear localization of a version of the full-length protein predominant in medium spiny neurons, and subsequent formation of N-terminal inclusions and insoluble aggregate.

TL;DR: It is demonstrated that HD disease modification in humans occurs in nature and offer a genetic route to identifying in-human validated therapeutic targets in this and other Mendelian disorders.

TL;DR: The generation and characterization of 14 induced pluripotent stem cell (iPSC) lines from HD patients and controls reveal CAG-repeat-expansion-associated gene expression patterns that distinguish patient lines from controls, and early onset versus late onset HD.

TL;DR: The results indicate that gametogenesis is the primary source of inherited instability in the Hdh knock-in mouse, but that the underlying repeat length-dependent mechanism, which may or may not be related in the two species, operates at higher CAG numbers.