NR ARPV
AU Hafezparast,M.; Brandner,S.; Linehan,J.; Martin,J.E.; Collinge,J.; Fisher,E.M.C.
TI Prion disease incubation time is not affected in mice heterozygous for a dynein mutation
QU Biochemical and Biophysical Research Communications 2004 Dec 31; 326(1): 18-22
PT journal article
AB A mechanism for transmission of the infectious prions from the peripheral nerve ends to the central nervous system is thought to involve neuronal anterograde and retrograde transport systems. Cytoplasmic dynein is the major retrograde transport molecular motor whose function is impaired in the Legs at odd angles (Loa) mouse due to a point mutation in the cytoplasmic dynein heavy chain subunit. Loa is a dominant trait which causes neurodegeneration and progressive motor function deficit in the heterozygotes. To investigate the role of cytoplasmic dynein in the transmission of prions within neurons, we inoculated heterozygous Loa and wild type littermates with mouse-adapted scrapie prions intracerebrally and intraperitonially, and determined the incubation period to onset of clinical prion disease. Our data indicate that the dynein mutation in the heterozygous state does not affect prion disease incubation time or its neuropathology in Loa mice.
MH Animals; Axons/*metabolism; Biological Transport, Active; Brain/*metabolism; Disease Progression; Disease-Free Survival; Dynein ATPase/*deficiency; Heterozygote; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Mutation; Prions/administration & dosage/*metabolism/*pathogenicity; Research Support, Non-U.S. Gov't; Scrapie/*transmission; Survival Analysis
AD Department of Neurodegenerative Disease, Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK. m.hafezparast@sussex.ac.uk
SP englisch
PO USA