{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T17:06:09Z","timestamp":1791824769059,"version":"4.3.4"},"reference-count":31,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5620","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2003,5,2]]},"abstract":"<jats:p>Degenerative disorders of motor neurons include a range of progressive fatal diseases such as amyotrophic lateral sclerosis (ALS), spinal-bulbar muscular atrophy (SBMA), and spinal muscular atrophy (SMA). Although the causative genetic alterations are known for some cases, the molecular basis of many SMA and SBMA-like syndromes and most ALS cases is unknown. Here we show that missense point mutations in the cytoplasmic dynein heavy chain result in progressive motor neuron degeneration in heterozygous mice, and in homozygotes this is accompanied by the formation of Lewy-like inclusion bodies, thus resembling key features of human pathology. These mutations exclusively perturb neuron-specific functions of dynein.<\/jats:p>","DOI":"10.1126\/science.1083129","type":"journal-article","created":{"date-parts":[[2003,5,1]],"date-time":"2003-05-01T16:53:52Z","timestamp":1051808032000},"page":"808-812","source":"Crossref","is-referenced-by-count":604,"title":["Mutations in Dynein Link Motor Neuron Degeneration to Defects in Retrograde Transport"],"prefix":"10.1126","volume":"300","author":[{"given":"Majid","family":"Hafezparast","sequence":"first","affiliation":[{"name":"Department of Neurodegenerative Disease, Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK."},{"name":"Ingenium Pharmaceuticals AG, Fraunhoferstrasse 13, 82152 Martinsried, Munich, Germany."},{"name":"Cancer Research UK, Laboratories of Endothelial Cell Biology, Cell Regulation and Molecular Neuropathobiology, 44 Lincoln's Inn Fields, London WC2A 3PX, UK."},{"name":"Department of Histopathology, Queen Mary University of London, The Royal London Hospital, Whitechapel, London E1 1BB, UK."},{"name":"Department of Neuroscience, Barts and The London, Queen Mary University of London, London E1 4NS, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Klocke","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease, Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK."},{"name":"Ingenium Pharmaceuticals AG, Fraunhoferstrasse 13, 82152 Martinsried, Munich, Germany."},{"name":"Cancer Research UK, Laboratories of Endothelial Cell Biology, Cell Regulation and Molecular Neuropathobiology, 44 Lincoln's Inn Fields, London WC2A 3PX, UK."},{"name":"Department of Histopathology, Queen Mary University of London, The Royal London Hospital, Whitechapel, London E1 1BB, UK."},{"name":"Department of Neuroscience, Barts and The London, Queen Mary University of London, London E1 4NS, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiana","family":"Ruhrberg","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease, Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK."},{"name":"Ingenium Pharmaceuticals AG, Fraunhoferstrasse 13, 82152 Martinsried, Munich, Germany."},{"name":"Cancer Research UK, Laboratories of Endothelial Cell Biology, Cell Regulation and Molecular Neuropathobiology, 44 Lincoln's Inn Fields, London WC2A 3PX, UK."},{"name":"Department of Histopathology, Queen Mary University of London, The Royal London Hospital, Whitechapel, London E1 1BB, UK."},{"name":"Department of Neuroscience, Barts and The London, Queen Mary University of London, London E1 4NS, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Marquardt","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease, Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK."},{"name":"Ingenium Pharmaceuticals AG, Fraunhoferstrasse 13, 82152 Martinsried, Munich, Germany."},{"name":"Cancer Research UK, Laboratories of Endothelial Cell Biology, Cell Regulation and Molecular Neuropathobiology, 44 Lincoln's Inn Fields, London WC2A 3PX, UK."},{"name":"Department of Histopathology, Queen Mary University of London, The Royal London Hospital, Whitechapel, London E1 1BB, UK."},{"name":"Department of Neuroscience, Barts and The London, Queen Mary University of London, London E1 4NS, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azlina","family":"Ahmad-Annuar","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease, Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK."},{"name":"Ingenium Pharmaceuticals AG, Fraunhoferstrasse 13, 82152 Martinsried, 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