Year: 2020
Type: preprint
Abstract: Expanded trinucleotide repeats cause many human diseases, including Huntington’s 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.
Authors: Sydney R. Coffey, Marissa Andrew, Heather Ging, Joseph Hamilton, Michael Flower, Marina Kovalenko, Robert M. Bragg, Jeffrey P. Cantle, Cassandra A. McHugh, José M. Carrillo, Julie-Anne Rodier, Deanna M. Marchionini, Hilary A. Wilkinson, Seung Kwak, David S. Howland, C. Frank Bennett, Ricardo Mouro Pinto, Georg Auburger, Scott O. Zeitlin, Holly B. Kordasiewicz, Sarah J. Tabrizi, Vanessa C. Wheeler, Jeffrey B. Carroll
Institutions: Western Washington University, Massachusetts General Hospital, UK Dementia Research Institute, UCL Queen Square Institute of Neurology, University College London, CHDI Foundation, Ionis Pharmaceuticals (United States), Harvard University, Goethe University Frankfurt, University of Virginia
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3044732590