ArticleMolecular therapy : the journal of the American Society of Gene Therapy2010
Rescue of a dystrophin-like protein by exon skipping in vivo restores GABAA-receptor clustering in the hippocampus of the mdx mouse.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed, 57 citations in OpenAlex.
- Ineffective behavioral rescue despite partial brain Dp427 restoration by AAV9-U7-mediated exon 51 skipping inMolecular therapy. Nucleic acids · 2025Article
- Behavioral improvement in dystrophicMolecular therapy. Nucleic acids · 2025Article
- Conditional Dmd ablation in muscle and brain causes profound effects on muscle function and neurobehavior.Communications biology · 2025Article
- Central Neurophysiological Alterations in Dystrophic mdx Mice Correlate With Reduced Hippocampal Levels of the Endogenous NMDA Receptor Ligand D-Aspartate.Journal of neurochemistry · 2025Article
- Understanding Duchenne muscular dystrophy-associated brain pathology.Disease models & mechanisms · 2025Review
- Neuronal hyperexcitability in dystrophin-deficient mdx hippocampal neurons: the importance of interleukin-6 and GABAergic regulation.Scientific reports · 2025Article
- The role of dystrophin isoforms and interactors in the brain.Brain : a journal of neurology · 2025Review
- Astrocyte proliferation in the hippocampal dentate gyrus is suppressed across the lifespan of dystrophin-deficient mdx mice.Experimental physiology · 2025Article
- Startle responses in Duchenne muscular dystrophy: a novel biomarker of brain dystrophin deficiency.Brain : a journal of neurology · 2023Observational
- Abnormal Expression of Synaptic and Extrasynaptic GABAInternational journal of molecular sciences · 2022Article
- Validation of DE50-MD dogs as a model for the brain phenotype of Duchenne muscular dystrophy.Disease models & mechanisms · 2022Article
- Article
- Disrupted Calcium Homeostasis in Duchenne Muscular Dystrophy: A Common Mechanism behind Diverse Consequences.International journal of molecular sciences · 2021Review
- Emotional behavior and brain anatomy of the mdx52 mouse model of Duchenne muscular dystrophy.Disease models & mechanisms · 2021Article
- Rescue of Defective Electroretinographic Responses in Dp71-Null Mice With AAV-Mediated Reexpression of Dp71.Investigative ophthalmology & visual science · 2020Article
- Characterization of brain dystrophins absence and impact in dystrophin-deficient Dmdmdx rat model.PloS one · 2020Article
- Essential role for InSyn1 in dystroglycan complex integrity and cognitive behaviors in mice.eLife · 2019Article
- Dp71-Dystrophin Deficiency Alters Prefrontal Cortex Excitation-Inhibition Balance and Executive Functions.Molecular neurobiology · 2019Article
- Molecular Specialization of GABAergic Synapses on the Soma and Axon in Cortical and Hippocampal Circuit Function and Dysfunction.Frontiers in molecular neuroscience · 2019Article
- Cerebellar synapse properties and cerebellum-dependent motor and non-motor performance inDisease models & mechanisms · 2018Article
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dystrophin, the cytoskeletal protein whose defect is responsible for Duchenne muscular dystrophy (DMD), is normally expressed in both muscles and brain. Genetic loss of brain dystrophin in the mdx mouse model of DMD reduces the capacity for type A gamma-aminobutyric acid (GABA(A))-receptor clustering in central inhibitory synapses, which is thought to be a main molecular defect leading to brain and cognitive alterations in this syndrome. U7 small nuclear RNAs modified to encode antisense sequences and expressed from recombinant adeno-associated viral (rAAV) vectors have proven efficient after intramuscular injection to induce skipping of the mutated exon 23 and rescue expression of a functional dystrophin-like product in muscle tissues of mdx mice in vivo. Here, we report that intrahippocampal injection of a single dose of rAAV2/1-U7 can rescue substantial levels of brain dystrophin expression (15-25%) in mdx mice for months. This is sufficient to completely restore GABA(A)-receptor clustering in pyramidal and dendritic layers of CA1 hippocampus, suggesting exon-skipping strategies offer the prospect to investigate and correct both brain and muscle alterations in DMD. This provides new evidence that in the adult brain dystrophin is critical for the control of GABA(A)-receptor clustering, which may have an important role in activity-dependent synaptic plasticity in hippocampal circuits.
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