Motor dysfunction and neurodegeneration in a C9orf72 mouse line expressing poly-PR.

ABSTRACT: A GGGGCC hexanucleotide repeat expansion in intron 1 of chromosome 9 open reading frame 72 (C9ORF72) gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Repeat-associated non-ATG translation of dipeptide repeat proteins (DPRs) contributes to the neuropathological features of c9FTD/ALS. Among the five DPRs, arginine-rich poly-PR are reported to be the most toxic. Here, we generate a transgenic mouse line that expresses poly-PR (GFP-PR₂₈) specifically in neurons. GFP-PR₂₈ homozygous mice show decreased survival time, while the heterozygous mice show motor imbalance, decreased brain weight, loss of Purkinje cells and lower motor neurons, and inflammation in the cerebellum and spinal cord. Transcriptional analysis show

SUBMITTER: Hao Z 

PROVIDER: S-EPMC6606620 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature