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Huntingtin lowering reduces somatic instability at CAG-expanded loci

Coffey, S. R.; Andrew, M.; Ging, H.; Hamilton, J.; Flower, M.; Kovalenko, M.; Bragg, R. M.; Cantle, J. P.; McHugh, C. A.; Carrillo, J. M.; Rodier, J.-A.; Marchionini, D. M.; Wilkinson, H. A.; Kwak, S.; Howland, D. S.; Bennett, C. F.; Mouro Pinto, R.; Auburger, G.; Zeitlin, S. O.; Kordasiewicz, H. B.; Tabrizi, S. J.; Wheeler, V. C.; Carroll, J. B.

2020-07-25 neuroscience
10.1101/2020.07.23.218347 bioRxiv
Show abstract

Expanded trinucleotide repeats cause many human diseases, including Huntingtons disease (HD). Recent studies indicate that somatic instability of these repeats contributes to pathogenesis in several expansion disorders. We find that lowering huntingtin protein (HTT) levels reduces somatic instability of both the Htt and Atxn2 CAG tracts in knockin mouse models, and the HTT CAG tract in human iPSC-derived neurons, revealing an unexpected role for HTT in regulating somatic instability.

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