ArticleDisease models & mechanisms
An ENU-induced mutation in mouse glycyl-tRNA synthetase (GARS) causes peripheral sensory and motor phenotypes creating a model of Charcot-Marie-Tooth type 2D peripheral neuropathy.
Article in Disease models & mechanisms. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 100 citations in OpenAlex.
- The neuropathy-causingbioRxiv : the preprint server for biology · 2026Article
- 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
- Glycyl-tRNA sequestration is a unifying mechanism underlying GARS1-associated peripheral neuropathy.Nucleic acids research · 2025Article
- A model organism pipeline provides insight into the clinical heterogeneity of TARS1 loss-of-function variants.HGG advances · 2024Article
- Mechanisms and Delivery of tRNA Therapeutics.Chemical reviews · 2024Review
- Lack of effect from genetic deletion of Hdac6 in a humanized mouse model of CMT2D.Journal of the peripheral nervous system : JPNS · 2024Article
- Predictive modeling provides insight into the clinical heterogeneity associated withbioRxiv : the preprint server for biology · 2024Article
- Boosting BDNF in muscle rescues impaired axonal transport in a mouse model of DI-CMTC peripheral neuropathy.bioRxiv : the preprint server for biology · 2024Article
- Article
- An Adapted GeneSwitch Toolkit for Comparable Cellular and Animal Models: A Proof of Concept in Modeling Charcot-Marie-Tooth Neuropathy.International journal of molecular sciences · 2023Article
- A humanized yeast model reveals dominant-negative properties of neuropathy-associated alanyl-tRNA synthetase mutations.Human molecular genetics · 2023Article
- Large-scale detection and characterization of interchromosomal rearrangements in normozoospermic bulls using massive genotype and phenotype data sets.Genome research · 2023Article
- Article
- NMJ-related diseases beyond the congenital myasthenic syndromes.Frontiers in cell and developmental biology · 2023Review
- Dominant aminoacyl-tRNA synthetase disorders: lessons learned fromFrontiers in neuroscience · 2023Review
- NCAM1 and GDF15 are biomarkers of Charcot-Marie-Tooth disease in patients and mice.Brain : a journal of neurology · 2022Article
- Immunoprecipation Assay to Quantify the Amount of tRNAs associated with Their Interacting Proteins in Tissue and Cell Culture.Bio-protocol · 2022Article
- HDAC6 Inhibition Corrects Electrophysiological and Axonal Transport Deficits in a Human Stem Cell-Based Model of Charcot-Marie-Tooth Disease (Type 2D).Advanced biology · 2022Article
- Conformational sampling of CMT-2D associated GlyRS mutations.Brain multiphysics · 2022Article
- Review
16 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 7 institutions in 3 countries.
Funding
Abstract
Mutations in the enzyme glycyl-tRNA synthetase (GARS) cause motor and sensory axon loss in the peripheral nervous system in humans, described clinically as Charcot-Marie-Tooth type 2D or distal spinal muscular atrophy type V. Here, we characterise a new mouse mutant, Gars(C201R), with a point mutation that leads to a non-conservative substitution within GARS. Heterozygous mice with a C3H genetic background have loss of grip strength, decreased motor flexibility and disruption of fine motor control; this relatively mild phenotype is more severe on a C57BL/6 background. Homozygous mutants have a highly deleterious set of features, including movement difficulties and death before weaning. Heterozygous animals have a reduction in axon diameter in peripheral nerves, slowing of nerve conduction and an alteration in the recovery cycle of myelinated axons, as well as innervation defects. An assessment of GARS levels showed increased protein in 15-day-old mice compared with controls; however, this increase was not observed in 3-month-old animals, indicating that GARS function may be more crucial in younger animals. We found that enzyme activity was not reduced detectably in heterozygotes at any age, but was diminished greatly in homozygous mice compared with controls; thus, homozygous animals may suffer from a partial loss of function. The Gars(C201R) mutation described here is a contribution to our understanding of the mechanism by which mutations in tRNA synthetases, which are fundamentally important, ubiquitously expressed enzymes, cause axonopathy in specific sets of neurons.
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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.