NR ADDY
AU DeArmond,S.J.; Yang,S.L.; Cayetano-Canlas,J.; Groth,D.; Prusiner,S.B.
TI The neuropathological phenotype in transgenic mice expressing different prion protein constructs
QU Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 1994 Mar 29; 343(1306): 415-23
IA http://www.journals.royalsoc.ac.uk/(pkuksk45ynsqzt45ifpjlf45)/app/home/contribution.asp?referrer=parent&backto=issue,11,16;journal,171,225;linkingpublicationresults,1:102022,1
PT journal article; review; review, tutorial
AB Neuropathologic examination of transgenic (Tg) mice which express different prion protein (PrP) constructs is essential because spongiform (vacuolar) degeneration of neurons, the distribution of PrPsc and whether PrP amyloid plaques form are the phenotypes of prion diseases. In Tg models of experimental scrapie, it was found that all of the parameters that define prion isolates ('strains') can be manipulated by changing the structure of PrP. In those studies, further evidence that PrPsc causes scrapie neuropathology and determines scrapie incubation time was obtained. In addition, the distribution of PrPsc in the brain was unique for each prion isolate. The implications of these findings are first, that prion isolates target different neuron populations for synthesis of nascent pathogenic PrPsc and, secondly, that prion isolate diversity is determined by neurons. In Tg mice which express mutated PrP mimicking human prion protein gene mutations linked to familial prion diseases, the neuropathological changes have been faithfully reproduced. A new age-related, neuromuscular disorder has also been identified in uninfected Tg mice which overexpress wild-type PrPc. All of the findings with different PrP constructs plus the absence of scrapie pathology in PrP null mice are the strongest argument that the prion protein is the main etiologic and pathogenic factor of prion disorders.
IN Es gibt Prionstämme, die in mehreren Punkten etwas unterschiedliche Krankheitsbilder verursachen. Diese Parameter lassen sich alle durch gezielte Mutationen des Prionproteins manipulieren. Demnach spricht die Existenz verschiedener Scrapiestämme nicht gegen die Theorie von Prionproteinen als neuartigen Krankheitserregern. Unterschiedliche Prionproteine haben verschiedene Hauptzielorte im Gehirn, wobei die Selektivität von den unterschiedlichen Neuronen abzuhängen scheint. In Mäusen mit einer Überexpression von normalen Prionproteinen entwickelt sich im Alter eine neuromuskuläre Erkrankung.
ZR 49
MH Age Factors; Animal; Brain/metabolism/pathology; Creutzfeldt-Jakob Syndrome/genetics; Disease Models, Animal; Human; Mice; Mice, Transgenic; Phenotype; PrPsc Proteins; Prion Diseases/*genetics/metabolism/pathology; Prions/*genetics/metabolism; Scrapie/genetics/metabolism/pathology
AD Department of Pathology (Neuropathology), University of California, San Francisco 94143.
SP englisch
PO England