ArticlePLoS genetics2015
Lack of GDAP1 induces neuronal calcium and mitochondrial defects in a knockout mouse model of charcot-marie-tooth neuropathy.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions.Nature genetics · 2023Pooled it
- 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
- Unraveling GDAP1: Bridging Mitochondrial Biology and Peripheral Neuropathy.Biomolecules · 2026Review
- Genetic basis of Charcot-Marie-Tooth disease in Pakistani consanguineous families.Frontiers in neurology · 2026Article
- Expression of GDAP1 Gene Correlates With Alcohol Deprivation Effect.Genes, brain, and behavior · 2025Article
- Abnormal redox balance at membrane contact sites causes axonopathy inResearch square · 2024Article
- Readthrough Activators and Nonsense-Mediated mRNA Decay Inhibitor Molecules: Real Potential in Many Genetic Diseases Harboring Premature Termination Codons.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Intravenous Administration of an AAV9 Vector Ubiquitously Expressing C1orf194 Gene Improved CMT-Like Neuropathy in C1orf194Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- Rapid degeneration of iPSC-derived motor neurons lacking Gdap1 engages a mitochondrial-sustained innate immune response.Cell death discovery · 2023Article
- Differential effects of Mendelian GDAP1 clinical variants on mitochondria-lysosome membrane contacts sites.Biology open · 2023Article
- Conserved intramolecular networks in GDAP1 are closely connected to CMT-linked mutations and protein stability.PloS one · 2023Article
- Distinct roles for the Charcot-Marie-Tooth disease-causing endosomal regulators Mtmr5 and Mtmr13 in axon radial sorting and Schwann cell myelination.Human molecular genetics · 2022Article
- Effective therapeutic strategies in a preclinical mouse model of Charcot-Marie-Tooth disease.Human molecular genetics · 2021Article
- Animal Models as a Tool to Design Therapeutical Strategies for CMT-like Hereditary Neuropathies.Brain sciences · 2021Review
- GDAP1 Involvement in Mitochondrial Function and Oxidative Stress, Investigated in a Charcot-Marie-Tooth Model of hiPSCs-Derived Motor Neurons.Biomedicines · 2021Article
- Review
- Molecular Mechanisms behind Inherited Neurodegeneration of the Optic Nerve.Biomolecules · 2021Review
- Mitochondria-lysosome membrane contacts are defective in GDAP1-related Charcot-Marie-Tooth disease.Human molecular genetics · 2021Article
- Mutations inInternational journal of molecular sciences · 2021Article
- Novel compound heterozygous missense mutations inJournal of genetics · 2021Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in GDAP1, which encodes protein located in the mitochondrial outer membrane, cause axonal recessive (AR-CMT2), axonal dominant (CMT2K) and demyelinating recessive (CMT4A) forms of Charcot-Marie-Tooth (CMT) neuropathy. Loss of function recessive mutations in GDAP1 are associated with decreased mitochondrial fission activity, while dominant mutations result in impairment of mitochondrial fusion with increased production of reactive oxygen species and susceptibility to apoptotic stimuli. GDAP1 silencing in vitro reduces Ca2+ inflow through store-operated Ca2+ entry (SOCE) upon mobilization of endoplasmic reticulum (ER) Ca2+, likely in association with an abnormal distribution of the mitochondrial network. To investigate the functional consequences of lack of GDAP1 in vivo, we generated a Gdap1 knockout mouse. The affected animals presented abnormal motor behavior starting at the age of 3 months. Electrophysiological and biochemical studies confirmed the axonal nature of the neuropathy whereas histopathological studies over time showed progressive loss of motor neurons (MNs) in the anterior horn of the spinal cord and defects in neuromuscular junctions. Analyses of cultured embryonic MNs and adult dorsal root ganglia neurons from affected animals demonstrated large and defective mitochondria, changes in the ER cisternae, reduced acetylation of cytoskeletal α-tubulin and increased autophagy vesicles. Importantly, MNs showed reduced cytosolic calcium and SOCE response. The development and characterization of the GDAP1 neuropathy mice model thus revealed that some of the pathophysiological changes present in axonal recessive form of the GDAP1-related CMT might be the consequence of changes in the mitochondrial network biology and mitochondria-endoplasmic reticulum interaction leading to abnormalities in calcium homeostasis.
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