ArticleThe Journal of clinical investigation1997
Myonuclear apoptosis in dystrophic mdx muscle occurs by perforin-mediated cytotoxicity.
Article in The Journal of clinical investigation, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 175 citations in OpenAlex.
- Mitochondrial alterations and oxidative stress in an acute transient mouse model of muscle degeneration: implications for muscular dystrophy and related muscle pathologies.The Journal of biological chemistry · 2014Trial
- CTLA4-Ig reduces proliferation and inflammatory gene expression in muscle fibroblasts, corresponding to less fibrosis and inflammation inAmerican journal of physiology. Cell physiology · 2026Article
- Inflammation in a severe model of dystrophic cardiomyopathy contains a high proportion of T cells that contribute to onset of pathology.American journal of physiology. Heart and circulatory physiology · 2026Article
- Early Taurine Administration Decreases the Levels of Receptor-Interacting Serine/Threonine Protein Kinase 1 in the Duchenne Mouse ModelBrain sciences · 2025Article
- Is dystrophin immunogenicity a barrier to advancing gene therapy for Duchenne muscular dystrophy?Gene therapy · 2025Review
- Cytotoxic T-Lymphocyte-Associated Protein 4 Fused to a Modified Fragment of IgG1 Reduces Muscle Fiber Damage in a Model of Duchenne Muscular Dystrophy by Attenuating Proinflammatory Gene Expression in Myeloid Lineage Cells.The American journal of pathology · 2025Article
- Characteristics of nuclear architectural abnormalities of myotubes differentiated from LmnaIn vitro cellular & developmental biology. Animal · 2024Article
- Respiratory characterization of a humanized Duchenne muscular dystrophy mouse model.Respiratory physiology & neurobiology · 2024Article
- Review
- Cellular interplay in skeletal muscle regeneration and wasting: insights from animal models.Journal of cachexia, sarcopenia and muscle · 2023Review
- Cilostazol attenuates oxidative stress and apoptosis in the quadriceps muscle of the dystrophic mouse experimental model.International journal of experimental pathology · 2023Article
- Duchenne muscular dystrophy: disease mechanism and therapeutic strategies.Frontiers in physiology · 2023Review
- Mechanisms of Myofibre Death in Muscular Dystrophies: The Emergence of the Regulated Forms of Necrosis in Myology.International journal of molecular sciences · 2022Review
- Molecular feature of neutrophils in immune microenvironment of muscle atrophy.Journal of cellular and molecular medicine · 2022Review
- Biomimetic sponges improve muscle structure and function following volumetric muscle loss.Journal of biomedical materials research. Part A · 2021Article
- Shared and distinct mechanisms of skeletal muscle atrophy: A narrative review.Ageing research reviews · 2021Review
- The linkage between inflammation and fibrosis in muscular dystrophies: The axis autotaxin-lysophosphatidic acid as a new therapeutic target?Journal of cell communication and signaling · 2021Review
- The Role of Innate and Adaptive Immune Cells in Skeletal Muscle Regeneration.International journal of molecular sciences · 2021Review
- Cellular senescence-mediated exacerbation of Duchenne muscular dystrophy.Scientific reports · 2020Article
- Short-Term ONX-0914 Administration: Performance and Muscle Phenotype inInternational journal of environmental research and public health · 2020Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Myonuclear apoptosis is an early event in the pathology of dystrophin-deficient muscular dystrophy in the mdx mouse. However, events that initiate apoptosis in muscular dystrophy are unknown, and whether elimination of apoptosis can ameliorate subsequent muscle wasting remains a major question. We have tested the hypothesis that cytotoxic T-lymphocytes initiate myonuclear apoptosis in dystrophic muscle, and examined whether perforin-mediated cytotoxicity plays a role in the pathophysiology of muscular dystrophy. Mdx mice showed muscle invasion by cytotoxic T cells and helper T cells at the onset of histologically detectable muscle fiber pathology. At this time, perforin-expressing cells were also present at elevated concentration. Mdx mice depleted of CD8(+) cells showed a significant reduction of apoptotic myonuclei concentration and a reduction in necrosis, judged by macrophage invasion of muscle fibers. Double-mutant mice, deficient in dystrophin and perforin, showed nearly complete absence of myonuclear apoptosis, and a significant reduction in the concentration of macrophages in the connective tissue surrounding muscle fibers. However, muscle fiber invasion by macrophages was not reduced significantly in double mutant mice. Thus, cytotoxic T-lymphocytes contribute significantly to apoptosis and necrosis in mdx dystrophy, and perforin-mediated killing is primarily responsible for myonuclear apoptosis.
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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.