Isolation of two distinct prion strains from a scrapie-affected sheep

Kentaro Masujin1, Yujing Shu, Hiroyuki Okada

  • 1Prion Disease Research Center, National Institute of Animal Health, Tsukuba, Ibaraki, Japan.

Archives of Virology
|October 31, 2009
PubMed

Insights

This study used mice to investigate a recent Japanese scrapie case. Unique clinical signs in one mouse suggest the potential coexistence of distinct prion strains within a single sheep.

Area of Science:

  • Veterinary Neurology
  • Prion Diseases
  • Animal Models

Background:

  • Scrapie is a fatal neurodegenerative disease affecting sheep and goats.
  • Understanding prion strain diversity is crucial for disease control and pathogenesis research.
  • The most recent Japanese scrapie case provided an opportunity for detailed investigation.

Purpose of the Study:

  • To characterize the transmissibility and phenotypic diversity of a recent Japanese scrapie isolate.
  • To investigate the potential for co-circulating prion strains within a single affected sheep.
  • To establish a mouse model for studying scrapie pathogenesis and strain variation.

Main Methods:

  • Transmission of brain homogenate from a scrapie-affected sheep to mice.
  • Monitoring of clinical signs, including neurological symptoms and metabolic changes.
  • Serial passage of the agent in mice to observe phenotypic stability and evolution.
  • Detailed clinical and pathological assessment of affected mice.

Main Results:

  • Primary transmission to mice resulted in progressive neurological disease.
  • One mouse exhibited unusual obesity, polydipsia, and polyuria, distinct from other affected mice showing weight loss and hypokinesia.
  • Subsequent passages revealed distinct scrapie phenotypes, correlating with the initial observations.
  • The varied phenotypes suggest the presence of multiple prion strains in the original inoculum.

Conclusions:

  • The findings support the hypothesis that different prion strains can coexist within a single naturally infected sheep.
  • This study provides evidence for phenotypic diversity in scrapie isolates.
  • The mouse model is valuable for dissecting prion strain characteristics and their impact on disease presentation.