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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Mutations in dynein link motor neuron degeneration to defects in retrograde transport.

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.[1]


  1. Mutations in dynein link motor neuron degeneration to defects in retrograde transport. Hafezparast, M., Klocke, R., Ruhrberg, C., Marquardt, A., Ahmad-Annuar, A., Bowen, S., Lalli, G., Witherden, A.S., Hummerich, H., Nicholson, S., Morgan, P.J., Oozageer, R., Priestley, J.V., Averill, S., King, V.R., Ball, S., Peters, J., Toda, T., Yamamoto, A., Hiraoka, Y., Augustin, M., Korthaus, D., Wattler, S., Wabnitz, P., Dickneite, C., Lampel, S., Boehme, F., Peraus, G., Popp, A., Rudelius, M., Schlegel, J., Fuchs, H., Hrabe de Angelis, M., Schiavo, G., Shima, D.T., Russ, A.P., Stumm, G., Martin, J.E., Fisher, E.M. Science (2003) [Pubmed]
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