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Updated: Jan 22, 2026

Gait Analysis of Age-dependent Motor Impairments in Mice with Neurodegeneration
Published on: June 18, 2018
Motor dysfunction and neurodegeneration in a C9orf72 mouse line expressing poly-PR
Zongbing Hao1, Liu Liu1, Zhouteng Tao2
1Laboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Neuropsychiatric Diseases & Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, 215123, China.
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 shows that in the cerebellum, GFP-PR28 heterozygous mice show differential expression of genes related to synaptic transmission. Our findings show that GFP-PR28 transgenic mice partly model neuropathological features of c9FTD/ALS, and show a role for poly-PR in neurodegeneration.
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