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