| RRC ID |
88516
|
| 著者 |
Verdone BM, Cicardi ME, Wen X, Sriramoji S, Russell K, Markandaiah SS, Jensen BK, Krishnamurthy K, Haeusler AR, Pasinelli P, Trotti D.
|
| タイトル |
A mouse model with widespread expression of the C9orf72-linked glycine-arginine dipeptide displays non-lethal ALS/FTD-like phenotypes.
|
| ジャーナル |
Sci Rep
|
| Abstract |
Translation of the hexanucleotide G4C2 expansion associated with C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD) produces five different dipeptide repeat protein (DPR) species that can confer toxicity. There is yet much to learn about the contribution of a single DPR to disease pathogenesis. We show here that a short repeat length is sufficient for the DPR poly-GR to confer neurotoxicity in vitro, a phenomenon previously unobserved. This toxicity is also reported in vivo in our novel knock-in mouse model characterized by widespread central nervous system (CNS) expression of the short-length poly-GR. We observe sex-specific chronic ALS/FTD-like phenotypes in these mice, including mild motor neuron loss, but no TDP-43 mis-localization, as well as motor and cognitive impairments. We suggest that this model can serve as the foundation for phenotypic exacerbation through second-hit forms of stress.
|
| 巻・号 |
12(1)
|
| ページ |
5644
|
| 公開日 |
2022-4-4
|
| DOI |
10.1038/s41598-022-09593-z
|
| PII |
10.1038/s41598-022-09593-z
|
| PMID |
35379876
|
| PMC |
PMC8979946
|
| MeSH |
Amyotrophic Lateral Sclerosis* / metabolism
Animals
Arginine / genetics
C9orf72 Protein / genetics
C9orf72 Protein / metabolism
Dipeptides / metabolism
Female
Frontotemporal Dementia* / pathology
Glycine / genetics
Male
Mice
Phenotype
|
| リソース情報 |
| 実験動物マウス |
RBRC01828 |
