TY - JOUR A1 - Todd, T. W. AU - McEachin, Z. T. AU - Chew, J. AU - Burch, A. R. AU - Jansen-West, K. AU - Tong, J. M. AU - Yue, M. AU - Song, Y. P. AU - Castanedes-Casey, M. AU - Kurti, A. AU - Dunmore, J. H. AU - Fryer, J. D. AU - Zhang, Y. J. AU - San Millan Tejado, Beatriz AU - Teijeira Bautista, Susana AU - Arias Gómez, Manuel AU - Dickson, D. AU - Gendron, T. F. AU - Sobrido Gómez, María Jesús AU - Disney, M. D. AU - Bassell, G. J. AU - Rossoll, W. AU - Petrucelli, L. T1 - Hexanucleotide Repeat Expansions in c9FTD/ALS and SCA36 Confer Selective Patterns of Neurodegeneration In Vivo Y1 - 2020 SN - 2211-1247 UR - http://hdl.handle.net/20.500.11940/16702 AB - A G4C2 hexanucleotide repeat expansion in an intron of C9orf72 is the most common cause of frontal temporal dementia and amyotrophic lateral sclerosis (c9FTD/ALS). A remarkably similar intronic TG3C2 repeat expansion is associated with spinocerebellar ataxia 36 (SCA36). Both expansions are widely expressed, form RNA foci, and can undergo repeat-associated non-ATG (RAN) translation to form similar dipeptide repeat proteins (DPRs). Yet, these diseases result in the degeneration of distinct subsets of neurons. We show that the expression of these repeat expansions in mice is sufficient to recapitulate the unique features of each disease, including this selective neuronal vulnerability. Furthermore, only the G4C2 repeat induces the formation of aberrant stress granules and pTDP-43 inclusions. Overall, our results demonstrate that the pathomechanisms responsible for each disease are intrinsic to the individual repeat sequence, highlighting the importance of sequence-specific RNA-mediated toxicity in each disorder. KW - Humans KW - RNA KW - Neurons KW - Amyotrophic Lateral Sclerosis KW - Mice KW - Inclusion Bodies KW - DNA Repeat Expansion KW - Animals KW - Frontotemporal Dementia KW - Nuclear Proteins KW - ARN KW - proteínas nucleares KW - neuronas KW - expansión de las repeticiones de ADN KW - animales KW - humanos KW - esclerosis lateral amiotrófica KW - cuerpos de inclusión KW - demencia frontotemporal KW - ratones KW - Amyotrophic Lateral Sclerosis KW - Animals KW - DNA Repeat Expansion KW - Frontotemporal Dementia KW - Humans KW - Inclusion Bodies KW - Mice KW - Neurons KW - Nuclear Proteins KW - RNA KW - CHUS KW - CHUVI KW - IDIS ER -