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Updated: Aug 20, 2026
High-throughput Screening for Protein-based Inheritance in S. cerevisiae
Published on: August 8, 2017
Prion disease incubation time is not affected in mice heterozygous for a dynein mutation
Majid Hafezparast1, Sebastian Brandner, Jackie Linehan
1Department of Neurodegenerative Disease, Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK. m.hafezparast@sussex.ac.uk
Abstract:
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.
Insights
This study investigated how impaired motor proteins affect prion transmission in mice. The findings indicate that a specific dynein mutation does not alter prion disease progression or brain pathology.
Area of Science:
- Neuroscience
- Molecular Biology
- Prion Biology
Background:
- Prion diseases involve infectious proteins spreading through the nervous system.
- Neuronal transport systems are implicated in prion transmission from peripheral nerves to the central nervous system.
- Cytoplasmic dynein, a key retrograde motor protein, is essential for neuronal transport.
Purpose of the Study:
- To investigate the role of cytoplasmic dynein in prion transmission within neurons.
- To determine if impaired dynein function affects prion disease incubation period and neuropathology.
Main Methods:
- Inoculation of heterozygous Legs at odd angles (Loa) mice and wild-type littermates with mouse-adapted scrapie prions.
- Intracerebral and intraperitoneal routes of prion inoculation were used.
- Monitoring and determination of the incubation period to the onset of clinical prion disease.
Main Results:
- The cytoplasmic dynein mutation in the heterozygous Loa mouse model did not significantly affect the incubation period for prion disease.
- Neuropathological examination revealed no significant differences in disease severity or lesion distribution between Loa and wild-type mice.
- These findings suggest that retrograde axonal transport, as mediated by cytoplasmic dynein, may not be a critical factor in the central nervous system spread of this prion strain.
Conclusions:
- Impairment of cytoplasmic dynein function in the heterozygous state does not influence the incubation time or neuropathology of prion disease in Loa mice.
- The study suggests that other mechanisms might be involved in the intra-neuronal spread of prions.
- Further research is needed to fully elucidate the role of neuronal transport in prion pathogenesis.
