DNM2 -Charcot-Marie-Tooth neuropathy stems from disrupted Schwann cell function and shows limited therapeutic reversibility
Clicks: 6
ID: 327055
2026
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This
article has not been analysed, so there is no overall score —
reader engagement is measured and shown alongside.
Reader Engagement
Emerging Content
1.5
/100
6 views
5 readers
AI Quality Assessment
Not analyzed
Readership in this journal
EmergingRanked #121 of 130 articles by views in Brain communications
Most read
Least read
Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 130 in total.
Mint this article as an NFT
Not yet mintedCreate a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.
5
SUSD
one-off · no wallet required
Abstract
Abstract Dominant loss-of-function mutations in DNM2 cause Charcot-Marie-Tooth neuropathy characterized by sensory and motor deficits associated with myelin and/or axonal abnormalities and muscle atrophy. Increasing DNM2 activity from embryogenesis has been reported to ameliorate neuromuscular phenotypes in the Dnm2K562E/+ Charcot-Marie-Tooth mouse; however, this model displays predominantly muscle pathology and limited nerve involvement, precluding rigorous evaluation of neuropathic mechanisms and potential therapies. Here, we performed comprehensive behavioral, electrophysiological, histological and molecular analyses to characterize the Dnm2K562E/SC- mouse, which combines systemic heterozygosity for the common K562E mutation together with Schwann cell-specific deletion of wild-type Dnm2. This model faithfully reproduces key clinical and pathological features of DNM2-Charcot-Marie-Tooth, including motor deficits, reduced general force and coordination, and severe sensory and motor conduction deficits associated with axonal loss, demyelination, and inflammation. Mechanistically, we delineate a coherent pathological sequence that explains the profound functional deficits. In particular, a downregulation of the transcription factor EGR2, a master regulator of myelin gene expression, and of the myelin protein MPZ correlates with demyelination. To evaluate the therapeutic potential of DNM2 supplementation, post-symptomatic intrathecal delivery of AAV9-DNM2 driven by the Schwann cell-specific MPZ promoter was performed at 4 weeks. Although DNM2 expression increased in peripheral nerves (∼1.9-fold), no significant improvements were observed across behavioral, electrophysiological, structural, or molecular parameters. Together, these findings establish the Dnm2K562E/SC- mouse as a robust preclinical model, recapitulating key features of DNM2- Charcot-Marie-Tooth, and provides crucial insight into the biological and temporal constraints that must guide future therapeutic strategies for DNM2-Charcot-Marie-Tooth.
| Reference Key |
openalex_W7204944429
Use this key to autocite in the manuscript while using
SciMatic Manuscript Manager or Thesis Manager
|
|---|---|
| Authors | Marie Goret, Thomas Arbogast, Jocelyn Laporte |
| Journal | Brain communications |
| Year | 2026 |
| DOI |
10.1093/braincomms/fcag324
|
| URL | |
| Keywords | Keywords not found |
Citations
No citations found. To add a citation, contact the admin at info@scimatic.org
Comments
No comments yet. Be the first to comment on this article.