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Prions--infectious pathogens causing the spongiform encephalopathies
Abstract:
The novel properties of the scrapie and Creutzfeldt-Jakob disease (CJD) transmissible agents readily distinguish them from viruses and viroids; thus, they have been labeled "prions". The scrapie prion contains a protein(s) which is required for infectivity; recently a 27,000 to 30,000 MW protein which purifies with the prion has been identified. The similarities between the scrapie and CJD agents suggest that CJD is also caused by a prion. Recent studies show that the time courses of both scrapie and CJD are determined by an autosominal dominant gene denoted PID (prion incubation determinant). In congenic mice infected with CJD, PID appears to be located on chromosome 17 in the major histocompatibility complex (H-2) in the D-subregion. Further studies indicate that replication of the scrapie and CJD prions precedes the development of pathological change. These changes share many similarities with those found in a variety of degenerative neurological disorders of unknown etiology.
Insights
Novel infectious agents, prions, cause scrapie and Creutzfeldt-Jakob disease (CJD). A specific gene, prion incubation determinant (PID), influences disease progression and is located on chromosome 17 in mice.
Area of Science:
- Neurodegenerative diseases
- Transmissible spongiform encephalopathies
- Molecular biology
Background:
- Scrapie and Creutzfeldt-Jakob disease (CJD) are caused by unique transmissible agents termed prions.
- Prions differ from viruses and viroids due to their novel properties.
- A protein essential for infectivity has been identified within the scrapie prion.
Purpose of the Study:
- To investigate the nature of prion diseases, including scrapie and CJD.
- To identify the genetic factors influencing prion disease incubation periods.
- To determine the chromosomal location of genes associated with prion disease.
Main Methods:
- Biochemical purification of prion components.
- Genetic analysis in congenic mouse models.
- Mapping of the prion incubation determinant (PID) gene.
Main Results:
- A 27,000-30,000 MW protein co-purifies with infectious prions.
- The prion incubation determinant (PID) gene, an autosomal dominant gene, controls disease time courses for both scrapie and CJD.
- In CJD-infected mice, PID is localized to chromosome 17 within the H-2 D-subregion.
Conclusions:
- Scrapie and CJD are likely caused by prions, with CJD sharing similarities with scrapie.
- Prion replication precedes pathological changes in the brain.
- The identified genetic locus (PID) on chromosome 17 provides a target for understanding prion disease pathogenesis and may offer insights into other degenerative neurological disorders.