| Literature DB >> 25977373 |
Jeannie Chew1, Tania F Gendron2, Mercedes Prudencio2, Hiroki Sasaguri2, Yong-Jie Zhang2, Monica Castanedes-Casey2, Chris W Lee2, Karen Jansen-West2, Aishe Kurti2, Melissa E Murray2, Kevin F Bieniek1, Peter O Bauer2, Ena C Whitelaw2, Linda Rousseau2, Jeannette N Stankowski2, Caroline Stetler2, Lillian M Daughrity2, Emilie A Perkerson2, Pamela Desaro3, Amelia Johnston3, Karen Overstreet3, Dieter Edbauer4, Rosa Rademakers1, Kevin B Boylan3, Dennis W Dickson1, John D Fryer1, Leonard Petrucelli5.
Abstract
The major genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis is a G4C2 repeat expansion in C9ORF72. Efforts to combat neurodegeneration associated with "c9FTD/ALS" are hindered by a lack of animal models recapitulating disease features. We developed a mouse model to mimic both neuropathological and clinical c9FTD/ALS phenotypes. We expressed (G4C2)66 throughout the murine central nervous system by means of somatic brain transgenesis mediated by adeno-associated virus. Brains of 6-month-old mice contained nuclear RNA foci, inclusions of poly(Gly-Pro), poly(Gly-Ala), and poly(Gly-Arg) dipeptide repeat proteins, as well as TDP-43 pathology. These mouse brains also exhibited cortical neuron and cerebellar Purkinje cell loss, astrogliosis, and decreased weight. (G4C2)66 mice also developed behavioral abnormalities similar to clinical symptoms of c9FTD/ALS patients, including hyperactivity, anxiety, antisocial behavior, and motor deficits.Entities:
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Year: 2015 PMID： 25977373 PMCID： PMC4692360 DOI： 10.1126/science.aaa9344
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728