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SCID mouse spleen does not support scrapie agent replication
K I O'Rourke1, T P Huff, C W Leathers
1United States Department of Agriculture, Animal Disease Research Unit, Pullman, Washington 99164-7030.
Abstract:
BALB/c and severe combined immunodeficiency (SCID) mice were inoculated intracerebrally or intraperitoneally with scrapie agent strain ME7 to examine the role of functional lymphocytes and follicular dendritic cells in splenic infectivity and PrPSc accumulation. Intracerebrally inoculated BALB/c and SCID mice developed the clinical signs and microscopic lesions characteristic of scrapie. Spleens from terminally affected BALB/c mice contained PrPSc which was detectable by immunoblot analysis; SCID mouse spleens did not contain detectable PrPSc. SCID mouse spleens collected during the first 90 days after intraperitoneal infection contained neither infectivity nor PrPSc.
Insights
Functional lymphocytes are crucial for scrapie agent infectivity and PrPSc accumulation in mouse spleens. Severe combined immunodeficiency (SCID) mice lacking these cells showed no detectable PrPSc, highlighting their importance in prion disease progression.
Area of Science:
- Neuroimmunology
- Prion Disease Research
- Immunology
Background:
- Scrapie is a transmissible spongiform encephalopathy affecting sheep and goats.
- The accumulation of abnormal prion protein (PrPSc) is a hallmark of prion diseases.
- The role of the immune system, particularly lymphocytes and follicular dendritic cells, in prion pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the role of functional lymphocytes and follicular dendritic cells in splenic infectivity and PrPSc accumulation.
- To compare scrapie agent (strain ME7) progression in immunocompetent BALB/c mice and severe combined immunodeficiency (SCID) mice.
Main Methods:
- Intracerebral and intraperitoneal inoculation of BALB/c and SCID mice with scrapie agent strain ME7.
- Monitoring for clinical signs and microscopic lesions characteristic of scrapie.
- Immunoblot analysis of spleen tissues to detect PrPSc accumulation.
- Assessing splenic infectivity in SCID mice post-infection.
Main Results:
- Both BALB/c and SCID mice inoculated intracerebrally developed clinical signs and lesions of scrapie.
- PrPSc was detectable in spleens of terminally affected BALB/c mice but not in SCID mice.
- SCID mouse spleens showed neither infectivity nor PrPSc within 90 days of intraperitoneal infection.
Conclusions:
- Functional lymphocytes and follicular dendritic cells are essential for PrPSc accumulation and splenic infectivity in scrapie.
- The absence of these immune components in SCID mice prevents systemic prion spread and accumulation in the spleen.