ArticleProceedings of the National Academy of Sciences of the United States of America2009
SH3TC2/KIAA1985 protein is required for proper myelination and the integrity of the node of Ranvier in the peripheral nervous system.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 113 citations in OpenAlex.
- Compound heterozygous mutations of SH3TC2 in Charcot-Marie-Tooth disease type 4C patients.Journal of human genetics · 2019Trial
- 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
- Article
- Quantitation of the physicochemical properties of myelin using Nile Red fluorescence spectroscopy.Journal of neurochemistry · 2025Article
- Postnatal persistence of hippocampal Cajal-Retzius cells has a crucial role in the establishment of the hippocampal circuit.Development (Cambridge, England) · 2024Article
- AAV1.tMCK.NT-3 gene therapy improves phenotype inBrain communications · 2024Article
- Genetic Landscape ofFrontiers in genetics · 2024Article
- Mitf is a Schwann cell sensor of axonal integrity that drives nerve repair.Cell reports · 2023Article
- AAV9-mediated SH3TC2 gene replacement therapy targeted to Schwann cells for the treatment of CMT4C.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Neuropathy due to bi-allelic SH3TC2 variants: genotype-phenotype correlation and natural history.Brain : a journal of neurology · 2023Article
- A Systematic Compilation of Human SH3 Domains: A Versatile Superfamily in Cellular Signaling.Cells · 2023Review
- Canine models of Charcot-Marie-Tooth: MTMR2, MPZ, and SH3TC2 variants in golden retrievers with congenital hypomyelinating polyneuropathy.Neuromuscular disorders : NMD · 2023Article
- Cross-regional homeostatic and reactive glial signatures in multiple sclerosis.Acta neuropathologica · 2022Article
- Screening for SH3TC2 variants in Charcot-Marie-Tooth disease in a cohort of Chinese patients.Acta neurologica Belgica · 2022Article
- Pan-Cancer Analysis Reveals SH3TC2 as an Oncogene for Colorectal Cancer and Promotes Tumorigenesis via the MAPK Pathway.Cancers · 2022Article
- From Negative to Positive Diagnosis: Structural Variation Could Be the Second Mutation You Are Looking for in a Recessive Autosomal Gene.Journal of personalized medicine · 2022Article
- Up-Regulation of SH3TC2 Induced by YTHDF1 Predicts Poor Outcome and Facilitates Cell-Cycle Progress in Colorectal Cancer.Journal of oncology · 2022Article
- Mechanisms and Treatments in Demyelinating CMT.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Review
- Animal Models as a Tool to Design Therapeutical Strategies for CMT-like Hereditary Neuropathies.Brain sciences · 2021Review
- Novel homozygous mutations in Pakistani families with Charcot-Marie-Tooth disease.BMC medical genomics · 2021Article
Corrections and comments
- Erratum issuedKleine, Henning [added]; Luscher, Bernhard [added]
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Charcot-Marie-Tooth disease type 4C (CMT4C) is an early-onset, autosomal recessive form of demyelinating neuropathy. The clinical manifestations include progressive scoliosis, delayed age of walking, muscular atrophy, distal weakness, and reduced nerve conduction velocity. The gene mutated in CMT4C disease, SH3TC2/KIAA1985, was recently identified; however, the function of the protein it encodes remains unknown. We have generated knockout mice where the first exon of the Sh3tc2 gene is replaced with an enhanced GFP cassette. The Sh3tc2(DeltaEx1/DeltaEx1) knockout animals develop progressive peripheral neuropathy manifested by decreased motor and sensory nerve conduction velocity and hypomyelination. We show that Sh3tc2 is specifically expressed in Schwann cells and localizes to the plasma membrane and to the perinuclear endocytic recycling compartment, concordant with its possible function in myelination and/or in regions of axoglial interactions. Concomitantly, transcriptional profiling performed on the endoneurial compartment of peripheral nerves isolated from control and Sh3tc2(DeltaEx1/DeltaEx1) animals uncovered changes in transcripts encoding genes involved in myelination and cell adhesion. Finally, detailed analyses of the structures composed of compact and noncompact myelin in the peripheral nerve of Sh3tc2(DeltaEx1/DeltaEx1) animals revealed abnormal organization of the node of Ranvier, a phenotype that we confirmed in CMT4C patient nerve biopsies. The generated Sh3tc2 knockout mice thus present a reliable model of CMT4C neuropathy that was instrumental in establishing a role for Sh3tc2 in myelination and in the integrity of the node of Ranvier, a morphological phenotype that can be used as an additional CMT4C diagnostic marker.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.