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Mutations in Dynein Link Motor Neuron Degeneration to Defects in Retrograde Transport
journal contribution
posted on 2023-06-08, 06:16 authored by Majid HafezparastMajid Hafezparast, Rainer Klocke, Christiana Ruhrberg, Andreas Marquardt, Azlina Ahmad-Annuar, Samantha Bowen, Giovanna Lalli, Abi S Witherden, Holger Hummerich, Sharon Nicholson, P Jeffrey Morgan, Ravi Oozageer, John V Priestley, Sharon Averill, Von R King, Simon Ball, Jo Peters, Takashi Toda, Ayumu Yamamoto, Yasushi Hiraoka, Martin Augustin, Dirk Korthaus, Sigrid Wattler, Philipp Wabnitz, Carmen Dickneite, Stefan Lampel, Florian Boehme, Gisela Peraus, Andreas Popp, Martina Rudelius, Juergen Schlegel, Helmut Fuchs, Martin Hrabe de Angelis, Giampietro Schiavo, David T Shima, Andreas P Russ, Gabriele Stumm, Joanne E Martin, Elizabeth M C FisherDegenerative 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.
History
Publication status
- Published
Journal
ScienceISSN
0036-8075External DOI
Issue
5620Volume
300Page range
808-812Pages
5.0Department affiliated with
- Neuroscience Publications
Notes
MH carried out the analysis and co-authored the paper in collaboration with three laboratories in the UK and one in Germany. This paper shows point mutations in cytoplasmic dynein resulting in defective retrograde axonal transport lead to motor neuron degeneration.Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06Usage metrics
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