Authors
Owen M Peters, Gabriela Toro Cabrera, Helene Tran, Tania F Gendron, Jeanne E McKeon, Jake Metterville, Alexandra Weiss, Nicholas Wightman, Johnny Salameh, Juhyun Kim, Huaming Sun, Kevin B Boylan, Dennis Dickson, Zachary Kennedy, Ziqiang Lin, Yong-Jie Zhang, Lillian Daughrity, Chris Jung, Fen-Biao Gao, Peter C Sapp, H Robert Horvitz, Daryl A Bosco, Solange P Brown, Pieter de Jong, Leonard Petrucelli, Christian Mueller, Robert H Brown
Publication date
2015/12/2
Journal
Neuron
Volume
88
Issue
5
Pages
902-909
Publisher
Cell Press
Description
A non-coding hexanucleotide repeat expansion in the C9ORF72 gene is the most common mutation associated with familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). To investigate the pathological role of C9ORF72 in these diseases, we generated a line of mice carrying a bacterial artificial chromosome containing exons 1 to 6 of the human C9ORF72 gene with approximately 500 repeats of the GGGGCC motif. The mice showed no overt behavioral phenotype but recapitulated distinctive histopathological features of C9ORF72 ALS/FTD, including sense and antisense intranuclear RNA foci and poly(glycine-proline) dipeptide repeat proteins. Finally, using an artificial microRNA that targets human C9ORF72 in cultures of primary cortical neurons from the C9BAC mice, we have attenuated expression of the C9BAC transgene and the poly(GP) dipeptides. The C9ORF72 BAC transgenic …
Scholar articles
OM Peters, GT Cabrera, H Tran, TF Gendron… - Neuron, 2015