Use of brain grafts to study the pathogenesis of prion diseases.
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.
Aguzzi
A
A
Department of Pathology, University of Zürich, Switzerland.
Klein
M A
MA
Musahl
C
C
Raeber
A J
AJ
Blättler
T
T
Hegyi
I
I
Frigg
R
R
Brandner
S
S
D000818:Animals; D001812:Blood-Brain Barrier; D016380:Brain Tissue Transplantation; D002490:Central Nervous System / Q000473:pathology; D004195:Disease Models, Animal; D016332:Fetal Tissue Transplantation; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D017096:Prion Diseases / Q000209:etiology* / Q000473:pathology / Q000635:transmission; D011328:Prions / Q000235:genetics / Q000472:pathogenicity; D012608:Scrapie / Q000209:etiology / Q000635:transmission
D011328:Prions