ArticleJournal of neuromuscular diseases2019
A Mutation in the Mitochondrial Aspartate/Glutamate Carrier Leads to a More Oxidizing Intramitochondrial Environment and an Inflammatory Myopathy in Dutch Shepherd Dogs.
Article in Journal of neuromuscular diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 16 citations in OpenAlex.
- SLC25A12 mitigates mitochondrial dysfunction in myoblast senescence, and alleviates cuproptosis-related changes under copper stress.Biology direct · 2026Article
- An inherited SLC25A12-related recessive form of congenital porencephaly in Limousin cattle.Genetics, selection, evolution : GSE · 2026Article
- Decoding Potential Cuproptosis-Related Genes in Sarcopenia: A Multi-Omics Network Analysis.Biology · 2025Article
- Polymyositis in Kooiker dogs is associated with a 39 kb deletion upstream of the canine IL21/IL2 locus.PLoS genetics · 2025Article
- Pathologic Changes in and Immunophenotyping of Polymyositis in the Dutch Kooiker Dog.Animals : an open access journal from MDPI · 2024Article
- Multi-Allelic Mitochondrial DNA Deletions in an Adult Dog with Chronic Weakness, Exercise Intolerance and Lactic Acidemia.Animals : an open access journal from MDPI · 2024Article
- Mitochondrial defects in sporadic inclusion body myositis-causes and consequences.Frontiers in cell and developmental biology · 2024Review
- An Inflammatory Myopathy in the Dutch Kooiker Dog.Animals : an open access journal from MDPI · 2023Article
- Tandem duplication within the DMD gene in Labrador retrievers with a mild clinical phenotype.Neuromuscular disorders : NMD · 2022Article
- AnGenes · 2022Article
- Article
- Congenital muscular dystrophy in a dog with a LAMA2 gene deletion.Journal of veterinary internal medicine · 2022Article
- An Overview of Mitochondrial Protein Defects in Neuromuscular Diseases.Biomolecules · 2021Review
- Muscular dystrophy-dystroglycanopathy in a family of Labrador retrievers with a LARGE1 mutation.Neuromuscular disorders : NMD · 2021Article
- Sarcoglycan A mutation in miniature dachshund dogs causes limb-girdle muscular dystrophy 2D.Skeletal muscle · 2021Article
- Diseases Caused by Mutations in Mitochondrial Carrier GenesBiomolecules · 2020Review
- Novel COL6A3 frameshift variant in American Staffordshire Terrier dogs with Ullrich-like congenital muscular dystrophy.Journal of veterinary internal medicineArticle
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInflammatory myopathies are characterized by infiltration of inflammatory cells into muscle. Typically, immune-mediated disorders such as polymyositis, dermatomyositis and inclusion body myositis are diagnosed.
objectiveA small family of dogs with early onset muscle weakness and inflammatory muscle biopsies were investigated for an underlying genetic cause.
methodsFollowing the histopathological diagnosis of inflammatory myopathy, mutational analysis including whole genome sequencing, functional transport studies of the mutated and wild-type proteins, and metabolomic analysis were performed.
resultsWhole genome resequencing identified a pathological variant in the SLC25A12 gene, resulting in a leucine to proline substitution at amino acid 349 in the mitochondrial aspartate-glutamate transporter known as the neuron and muscle specific aspartate glutamate carrier 1 (AGC1). Functionally reconstituting recombinant wild-type and mutant AGC1 into liposomes demonstrated a dramatic decrease in AGC1 transport activity and inability to transfer reducing equivalents from the cytosol into mitochondria. Targeted, broad-spectrum metabolomic analysis from affected and control muscles demonstrated a proinflammatory milieu and strong support for oxidative stress.
conclusionsThis study provides the first description of a metabolic mechanism in which ablated mitochondrial glutamate transport markedly reduced the import of reducing equivalents into mitochondria and produced a highly oxidizing and proinflammatory muscle environment and an inflammatory myopathy.
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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.