Omics · study · 2026
Gnal or Tor1a mutation leads to shared transcriptional alterations in striatal cellular subtypes in mouse models of dystonia
Listed in NCBI GEO
Dystonia is a hyperkinetic movement disorder characterized by sustained or intermittent muscle contraction and abnormal postures.
Description
Several dystonia-associated mutations have been identified. The common theme across the majority of studies utilizing animal models that recapitulate these mutations have indicated mechanisms of sustained, imperturbable long-term potentiation of corticostriatal synapses in medium spiny neurons (MSNs) and reduced ability to induce long-term depression.
This suggests a striato-centric neuronal adaptive response to mutation that may drive disease pathology. However, the cell type-specificity and molecular programs driving these changes are unknown. To address this, we utilized single-nucleus RNA-sequencing on striatal cells extracted from two dystonia mouse models that recapitulate genetic mutations linked to dystonia: DYT1 (Tor1awt/ E) and DYT25 (Gnal+/-).
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Upon analysis, MSNs exhibited the majority of transcriptional changes: Gnal deficiency was associated with downregulation of genes involved in the maintenance of membrane potential and increased expression of those encoding for neuron development-related molecules. Mice with Tor1awt/ E mutation had enhanced expression of specific immediate early genes (Arc and Npas4) in MSNs. These alterations may drive and/or reflect the altered plasticity mechanisms observed in dystonia.
Changes in transcription of several genes in MSNs were shared across both mouse models, including Lrrk2, Reln, and Pkrcb. Further exploration of these and other shared pathways may open new avenues for future investigation of strategies to treat dystonia and other conditions related to GNAL or TOR1A dysfunction.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE345nnn/GSE345347 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE345347 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1520123 ncbi.nlm.nih.gov/bioproject/PRJNA1520123 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Disease 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE345347 | 12 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |