ArticleHuman molecular genetics2013
Motor and sensory neuropathy due to myelin infolding and paranodal damage in a transgenic mouse model of Charcot-Marie-Tooth disease type 1C.
Article in Human molecular genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Junctions in Jeopardy: the neuromuscular junction is a selective pathological target in Charcot-Marie-Tooth disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- HDAC11 deficiency regulates age-related muscle decline and sarcopenia.GeroScience · 2025Article
- Morphometric analysis of peripheral nerves in people with spinal cord injury.Scientific reports · 2025Article
- High-Fat Diet Disrupt Nerve Function by Targeting Schwann Cells.Journal of the peripheral nervous system : JPNS · 2025Article
- Animal Models as a Tool to Design Therapeutical Strategies for CMT-like Hereditary Neuropathies.Brain sciences · 2021Review
- New evidence for secondary axonal degeneration in demyelinating neuropathies.Neuroscience letters · 2021Review
- A dysfunctional endolysosomal pathway common to two sub-types of demyelinating Charcot-Marie-Tooth disease.Acta neuropathologica communications · 2020Article
- Article
- Whole exome sequencing establishes diagnosis of Charcot-Marie-Tooth 4J, 1C, and X1 subtypes.Molecular genetics & genomic medicine · 2020Article
- Absence of Plekhg5 Results in Myelin Infoldings Corresponding to an Impaired Schwann Cell Autophagy, and a Reduced T-Cell Infiltration Into Peripheral Nerves.Frontiers in cellular neuroscience · 2020Article
- HERC1 Ubiquitin Ligase Is Required for Normal Axonal Myelination in the Peripheral Nervous System.Molecular neurobiology · 2018Article
- Integrated proteomics and network analysis identifies protein hubs and network alterations in Alzheimer's disease.Acta neuropathologica communications · 2018Article
- Muscle spindle alterations precede onset of sensorimotor deficits in Charcot-Marie-Tooth type 2E.Genes, brain, and behavior · 2017Article
- Dysregulation of ErbB Receptor Trafficking and Signaling in Demyelinating Charcot-Marie-Tooth Disease.Molecular neurobiology · 2017Review
- The topology, structure and PE interaction of LITAF underpin a Charcot-Marie-Tooth disease type 1C.BMC biology · 2016Article
- Morphology of Donor and Recipient Nerves Utilised in Nerve Transfers to Restore Upper Limb Function in Cervical Spinal Cord Injury.Brain sciences · 2016Article
- Palmoplantar keratoderma along with neuromuscular and metabolic phenotypes in Slurp1-deficient mice.The Journal of investigative dermatology · 2014Article
- Institutional animal care and use committee considerations for animal models of peripheral neuropathy.ILAR journal · 2014Review
- Node of Ranvier disruption as a cause of neurological diseases.ASN neuro · 2013Review
- SIMPLE: A new regulator of endosomal trafficking and signaling in health and disease.Communicative & integrative biology · 2013Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Charcot-Marie-Tooth disease type 1C (CMT1C) is a dominantly inherited motor and sensory neuropathy. Despite human genetic evidence linking missense mutations in SIMPLE to CMT1C, the in vivo role of CMT1C-linked SIMPLE mutations remains undetermined. To investigate the molecular mechanism underlying CMT1C pathogenesis, we generated transgenic mice expressing either wild-type or CMT1C-linked W116G human SIMPLE. Mice expressing mutant, but not wild type, SIMPLE develop a late-onset motor and sensory neuropathy that recapitulates key clinical features of CMT1C disease. SIMPLE mutant mice exhibit motor and sensory behavioral impairments accompanied by decreased motor and sensory nerve conduction velocity and reduced compound muscle action potential amplitude. This neuropathy phenotype is associated with focally infolded myelin loops that protrude into the axons at paranodal regions and near Schmidt-Lanterman incisures of peripheral nerves. We find that myelin infolding is often linked to constricted axons with signs of impaired axonal transport and to paranodal defects and abnormal organization of the node of Ranvier. Our findings support that SIMPLE mutation disrupts myelin homeostasis and causes peripheral neuropathy via a combination of toxic gain-of-function and dominant-negative mechanisms. The results from this study suggest that myelin infolding and paranodal damage may represent pathogenic precursors preceding demyelination and axonal degeneration in CMT1C patients.
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