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Hyperactivity of Purkinje cell and motor deficits in C9orf72 knockout mice

Mol Cell Neurosci. 2022-07; 
Yuning Liu, Hong Xing, Alexis F Ernst, Canna Liu, Christian Maugee, Fumiaki Yokoi, Madepalli Lakshmana, Yuqing Li
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摘要

A hexanucleotide (GGGGCC) repeat expansion in the first intron of the C9ORF72 gene is the most frequently reported genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The cerebellum has not traditionally been thought to be involved in the pathogenesis of C9ORF72-associated ALS/FTD, but recent evidence suggested a potential role. C9ORF72 is highly expressed in the cerebellum. Decreased C9ORF72 transcript and protein levels were detected in the postmortem cerebellum, suggesting a loss-of-function effect of C9ORF72 mutation. This study investigated the role of loss of C9ORF72 function using a C9orf72 knockout mouse line. C9orf72 deficiency led to motor impairment in rotarod, bea... More

关键词

BK channel, C9orf72, Hyperactivity, Motor behavior, Purkinje cell