Reference - Detail
| RRC ID | 88516 |
|---|---|
| Author | Verdone BM, Cicardi ME, Wen X, Sriramoji S, Russell K, Markandaiah SS, Jensen BK, Krishnamurthy K, Haeusler AR, Pasinelli P, Trotti D. |
| Title | A mouse model with widespread expression of the C9orf72-linked glycine-arginine dipeptide displays non-lethal ALS/FTD-like phenotypes. |
| Journal | 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. |
| Volume | 12(1) |
| Pages | 5644 |
| Published | 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 |
| IF | 3.998 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 7 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Mice | RBRC01828 |