| Literature DB >> 12730604 |
Majid Hafezparast1, 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.
Abstract
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.Entities:
Mesh：
Substances：
Year: 2003 PMID： 12730604 DOI： 10.1126/science.1083129
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728