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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 Fisher
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.

History

Publication status

  • Published

Journal

Science

ISSN

0036-8075

Issue

5620

Volume

300

Page range

808-812

Pages

5.0

Department 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

2012-02-06

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