RRC ID |
81243
|
Author |
Yoshioka N, Kurose M, Sano H, Tran DM, Chiken S, Tainaka K, Yamamura K, Kobayashi K, Nambu A, Takebayashi H.
|
Title |
Sensory-motor circuit is a therapeutic target for dystonia musculorum mice, a model of hereditary sensory and autonomic neuropathy 6.
|
Journal |
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.
|
Volume |
10(30)
|
Pages |
eadj9335
|
Published |
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
|
Resource |
Mice |
RBRC10246 |