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Shadoo (Sprn) and prion disease incubation time in mice
Sarah E Lloyd1, Julia Grizenkova, Hirva Pota
1MRC Prion Unit and Department of Neurodegenerative Diseases, UCL Institute of Neurology, London, UK. s.lloyd@prion.ucl.ac.uk
Abstract:
Prion diseases are transmissible neurodegenerative disorders of mammalian species and include scrapie, bovine spongiform encephalopathy (BSE), and variant Creutzfeldt-Jakob disease (vCJD). The prion protein (PrP) plays a key role in the disease, with coding polymorphism in both human and mouse influencing disease susceptibility and incubation time, respectively. Other genes are also thought to be important and a plausible candidate is Sprn, which encodes the PrP-like protein Shadoo (Sho). Sho is expressed in the adult central nervous system and exhibits neuroprotective activity reminiscent of PrP in an in vitro assay. To investigate the role of Sprn in prion disease incubation time we sequenced the open reading frame (ORF) in a diverse panel of mice and saw little variation except in strains derived from wild-trapped mice. Sequencing the untranslated regions revealed polymorphisms that allowed us to carry out an association study of incubation period in the Northport heterogeneous stock of mice inoculated with Chandler/RML prions. We also examined the expression level of Sprn mRNA in the brains of normal and prion-infected mice and saw no correlation with either genotype or incubation time. We therefore conclude that Sprn does not play a major role in prion disease incubation time in these strains of mice.
Insights
The Sprn gene, encoding the Shadoo protein, does not significantly influence prion disease incubation times in mice. Researchers found no major role for Sprn in prion disease progression in the studied mouse models.
Area of Science:
- Neurodegenerative diseases
- Prion biology
- Genetics of disease incubation
Background:
- Prion diseases are fatal neurodegenerative disorders affecting mammals.
- The prion protein (PrP) is central to disease pathogenesis.
- The PrP-like Shadoo (Sho) protein, encoded by Sprn, is expressed in the adult central nervous system and may have neuroprotective roles.
Purpose of the Study:
- To investigate the potential role of the Sprn gene in determining prion disease incubation time.
- To analyze genetic variation within the Sprn gene and its association with disease onset.
- To examine Sprn mRNA expression levels in prion-infected versus normal mouse brains.
Main Methods:
- Sequencing of the Sprn open reading frame (ORF) and untranslated regions in diverse mouse strains.
- Association study of Sprn polymorphisms with incubation period in mice inoculated with prions.
- Quantitative analysis of Sprn mRNA expression in mouse brain tissue.
Main Results:
- Limited genetic variation was found in the Sprn ORF, except in wild-derived strains.
- Polymorphisms in Sprn untranslated regions were identified and used in an association study.
- No significant correlation was observed between Sprn genotype or mRNA expression levels and prion disease incubation time.
Conclusions:
- The Sprn gene does not appear to play a major role in modulating prion disease incubation time in the studied mouse models.
- Further research may be needed to explore the function of Shadoo protein in other neurological contexts.
- These findings help refine our understanding of the genetic factors influencing prion disease pathogenesis.
