論文 - 詳細
| RRC ID | 81243 |
|---|---|
| 著者 | Yoshioka N, Kurose M, Sano H, Tran DM, Chiken S, Tainaka K, Yamamura K, Kobayashi K, Nambu A, Takebayashi H. |
| タイトル | Sensory-motor circuit is a therapeutic target for dystonia musculorum mice, a model of hereditary sensory and autonomic neuropathy 6. |
| ジャーナル | Sci Adv |
| Abstract |
Mutations in Dystonin (DST), which encodes cytoskeletal linker proteins, cause hereditary sensory and autonomic neuropathy 6 (HSAN-VI) in humans and the dystonia musculorum (dt) phenotype in mice; however, the neuronal circuit underlying the HSAN-VI and dt phenotype is unresolved. dt mice exhibit dystonic movements accompanied by the simultaneous contraction of agonist and antagonist muscles and postnatal lethality. Here, we identified the sensory-motor circuit as a major causative neural circuit using a gene trap system that enables neural circuit-selective inactivation and restoration of Dst by Cre-mediated recombination. Sensory neuron-selective Dst deletion led to motor impairment, degeneration of proprioceptive sensory neurons, and disruption of the sensory-motor circuit. Restoration of Dst expression in sensory neurons using Cre driver mice or a single postnatal injection of Cre-expressing adeno-associated virus ameliorated sensory degeneration and improved abnormal movements. These findings demonstrate that the sensory-motor circuit is involved in the movement disorders in dt mice and that the sensory circuit is a therapeutic target for HSAN-VI. |
| 巻・号 | 10(30) |
| ページ | eadj9335 |
| 公開日 | 2024-7-26 |
| DOI | 10.1126/sciadv.adj9335 |
| PMID | 39058787 |
| PMC | PMC11277474 |
| MeSH | Animals Dependovirus / genetics Disease Models, Animal* Dystonia / genetics Dystonin* / genetics Hereditary Sensory and Autonomic Neuropathies* / genetics Humans Mice Phenotype Sensory Receptor Cells* / metabolism |
| IF | 13.117 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC10246 |