ArticleGlia2017
Oligodendrocyte RasG12V expressed in its endogenous locus disrupts myelin structure through increased MAPK, nitric oxide, and notch signaling.
Article in Glia, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Genetic activation of ERK2 recapitulates core neurodevelopmental features of Rasopathy syndromes in mice.HGG advances · 2026Article
- Genetic activation of ERK2 recapitulates core neurodevelopmental features of Rasopathy syndromes in mice.bioRxiv : the preprint server for biology · 2025Article
- Current states in understanding oligodendroglia-mediated neurological issues in neurofibromatosis type 1 (NF1).Acta neuropathologica communications · 2025Review
- Hyperactivation of MEK1 in cortical glutamatergic neurons results in projection axon deficits and aberrant motor learning.Disease models & mechanisms · 2024Article
- Review
- Daam2 Regulates Myelin Structure and the Oligodendrocyte Actin Cytoskeleton through Rac1 and Gelsolin.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- A role for sustained MAPK activity in the mouse ventral telencephalon.Developmental biology · 2021Article
- Human Wharton's Jelly Mesenchymal Stromal Cell-Derived Small Extracellular Vesicles Drive Oligodendroglial Maturation by Restraining MAPK/ERK and Notch Signaling Pathways.Frontiers in cell and developmental biology · 2021Article
- Generation of a Mouse Model to Study the Noonan Syndrome GeneFrontiers in cell and developmental biology · 2021Article
- The sixth international RASopathies symposium: Precision medicine-From promise to practice.American journal of medical genetics. Part A · 2020Article
- The Noonan Syndrome-linked Raf1L613V mutation drives increased glial number in the mouse cortex and enhanced learning.PLoS genetics · 2019Article
- Perspectives of RAS and RHEB GTPase Signaling Pathways in Regenerating Brain Neurons.International journal of molecular sciences · 2018Review
- Three dimensional electron microscopy reveals changing axonal and myelin morphology along normal and partially injured optic nerves.Scientific reports · 2018Article
- Protection of Oligodendrocytes Through Neuronal Overexpression of the Small GTPase Ras in Hyperoxia-Induced Neonatal Brain Injury.Frontiers in neurology · 2018Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Costello syndrome (CS) is a gain of function Rasopathy caused by heterozygous activating mutations in the HRAS gene. Patients show brain dysfunction that can include abnormal brain white matter. Transgenic activation of HRas in the entire mouse oligodendrocyte lineage resulted in myelin defects and behavioral abnormalities, suggesting roles for disrupted myelin in CS brain dysfunction. Here, we studied a mouse model in which the endogenous HRas gene is conditionally replaced by mutant HRasG12V in mature oligodendrocytes, to separate effects in mature myelinating cells from developmental events. Increased myelin thickness due to decompaction was detectable within one month of HRasG12V expression in the corpus callosum of adult mice. Increases in active ERK and Nitric Oxide (NO) were present in HRas mutants and inhibition of NO synthase (NOS) or MEK each partially rescued myelin decompaction. In addition, genetic or pharmacologic inhibition of Notch signaling improved myelin compaction. Complete rescue of myelin structure required dual drug treatments combining MAPK, NO, or Notch inhibition; with MEK + NOS blockade producing the most robust effect. We suggest that individual or concomitant blockade of these pathways in CS patients may improve aspects of brain function.
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Registered trials
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.