Use of brain grafts to study the pathogenesis of prion diseases.

Abstract

For the study of prion neurotoxicity, we used neural-grafting techniques: mice devoid of the normal host prion protein (Prnp% mice) received a neural graft and were intracerebrally infected with mouse prions. The growth and differentiation properties of neural grafts were defined. Growth of embryonic neuroectodermal tissue was optimal at gestational days 12.5-13.5. The blood-brain barrier is reconstituted after 7 weeks in most animals. Scrapie-infected PrPC-expressing grafts develop a severe spongiform encephalopathy and contain proteinase-resistant protein and infectivity. Infected grafts deliver high amounts of prions to the host brain without eliciting disease. Infected grafts show a progressive disruption of the blood-brain barrier. Following intraocular prion inoculation of a transplanted Prnp% mouse, prions do not reach the intracerebral graft, indicating that PrP expression is required for propagation along the optic tract.

• Authors: A Aguzzi, M A Klein, C Musahl, A J Raeber, T Blättler, I Hegyi, R Frigg, S Brandner
• Journal: Essays in biochemistry (Essays Biochem) Vol. 33 Pg. 133-47 ( 1998) ISSN: 0071-1365 [Print] England
• PMID: 10488447 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Prions

Topics

• Animals
• Blood-Brain Barrier
• Brain Tissue Transplantation
• Central Nervous System (pathology)
• Disease Models, Animal
• Fetal Tissue Transplantation
• Humans
• Mice
• Mice, Knockout
• Prion Diseases (etiology, pathology, transmission)
• Prions (genetics, pathogenicity)
• Scrapie (etiology, transmission)