Mutations in Dynein Link Motor Neuron Degeneration to Defects in Retrograde Transport

Hafezparast, Majid, Klocke, Rainer, Ruhrberg, Christiana, Marquardt, Andreas, Ahmad-Annuar, Azlina, Bowen, Samantha, Lalli, Giovanna, Witherden, Abi S, Hummerich, Holger, Nicholson, Sharon, Morgan, P Jeffrey, Oozageer, Ravi, Priestley, John V, Averill, Sharon, King, Von R, Ball, Simon, Peters, Jo, Toda, Takashi, Yamamoto, Ayumu, Hiraoka, Yasushi, Augustin, Martin, Korthaus, Dirk, Wattler, Sigrid, Wabnitz, Philipp, Dickneite, Carmen, Lampel, Stefan, Boehme, Florian, Peraus, Gisela, Popp, Andreas, Rudelius, Martina, Schlegel, Juergen, Fuchs, Helmut, de Angelis, Martin Hrabe, Schiavo, Giampietro, Shima, David T, Russ, Andreas P, Stumm, Gabriele, Martin, Joanne E and Fisher, Elizabeth M C (2003) Mutations in Dynein Link Motor Neuron Degeneration to Defects in Retrograde Transport. Science, 300 (5620). pp. 808-812. ISSN 0036-8075

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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.

Item Type: Article
Additional Information: 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.
Schools and Departments: School of Life Sciences > Neuroscience
Depositing User: Majid Hafezparast
Date Deposited: 06 Feb 2012 20:26
Last Modified: 26 Mar 2012 12:58
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