In:
Science, American Association for the Advancement of Science (AAAS), Vol. 348, No. 6239 ( 2015-06-05), p. 1151-1154
Abstract:
The major genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis is a G 4 C 2 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 (G 4 C 2 ) 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. (G 4 C 2 ) 66 mice also developed behavioral abnormalities similar to clinical symptoms of c9FTD/ALS patients, including hyperactivity, anxiety, antisocial behavior, and motor deficits.
Type of Medium:
Online Resource
ISSN:
0036-8075
,
1095-9203
DOI:
10.1126/science.aaa9344
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2015
detail.hit.zdb_id:
128410-1
detail.hit.zdb_id:
2066996-3
detail.hit.zdb_id:
2060783-0
SSG:
11
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