NR AFDR
AU Harris,D.A.; Chiesa,R.; Drisaldi,B.; Quaglio,E.; Migheli,A.; Piccardo,P.; Ghetti,B.
TI A transgenic model of a familial prion disease
QU Archives of Virology. Supplementum 2000(16): 103-12
PT journal article; review; review, tutorial
AB We have generated lines of transgenic mice that express a mutant prion protein containing 14 octapeptide repeats whose human homologue is associated with an inherited prion dementia. These mice develop an ataxic illness that begins at 65 days of age when the transgene array is homozygous, and results in death by 115-138 days. Starting from birth, mutant PrP is converted into a protease-resistant and detergent-insoluble form that resembles PrPsc, and this form accumulates dramatically in many brain regions throughout the lifetime of the mice. As PrP accumulates, there is massive apoptosis of cerebellar granule cells, as well as astrocytosis and deposition of PrP in a punctate pattern. These results establish a new transgenic animal model of an inherited human prion disease, and provide important insights into the molecular pathogenesis of these disorders.
ZR 20
MH Animal; Brain/metabolism/pathology; *Disease Models, Animal; Human; Mice; *Mice, Transgenic; Mutation; PrPsc Proteins/chemistry/metabolism; *Prion Diseases/genetics/pathology/physiopathology; Prions/chemistry/*genetics/metabolism; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Transgenes
AD Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA
SP englisch
PO Österreich