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

• DOI: 10.1126/science.1083129
• Publication Date: 2003-05-01T20:53:52Z
• Authors: Majid 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 A...; Giampietro Schiavo; David T. Shima; Andreas P. Russ; Gabriele Stumm; Joanne E. Martin; Elizabeth M. C. F...
• Keywords: Degeneration (medical)

Degenerative disorders of motor neurons include a range progressive fatal diseases such as amyotrophic lateral sclerosis (ALS), spinal-bulbar muscular atrophy (SBMA), and spinal (SMA). Although the causative genetic alterations are known for some cases, molecular basis many SMA SBMA-like syndromes most ALS cases is unknown. Here we show that missense point mutations in cytoplasmic dynein heavy chain result neuron degeneration heterozygous mice, homozygotes this accompanied by formation Lewy-like inclusion bodies, thus resembling key features human pathology. These exclusively perturb neuron-specific functions dynein.