NR APNB
AU Weissmann,C.; Flechsig,E.
TI PrP knock-out and PrP transgenic mice in prion research
QU British Medical Bulletin 2003; 66: 43-60
PT journal article; review; review, tutorial
AB Spongiform encephalopathies such as scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle or Creutzfeldt-Jakob disease (CJD) and Gerstmann-Sträussler-Scheinker syndrome (GSS) in humans is caused by a transmissible agent designated prion. The 'protein only' hypothesis proposes that the prion consists partly or entirely of a conformational isoform of the normal host protein PrPc, designated PrP(*)(1) and that the abnormal conformer, when introduced into the organism, causes the conversion of PrPc into a likeness of itself. PrP(*) may be congruent with PrPsc, a protease-resistant, aggregated conformer of PrP that accumulates mainly in brain of almost all prion-infected organisms. PrPc consists of a flexible N-terminal half, comprising Cu(2+)-binding octapeptide repeats, and a globular domain consisting of three alpha-helices, one short antiparallel beta-sheet and a single disulphide bond. It is anchored at the outer cell-surface by a glycosyl phosphatidylinositol (GPI) tail and is present in almost all tissues, however, mainly in brain. Compelling linkage between the prion and PrP was established by biochemical and genetic data and led to the prediction that animals devoid of PrP should be resistant to experimental scrapie and fail to propagate infectivity. This prediction was indeed borne out, adding substantial support to the 'protein only' hypothesis. In addition, the availability of PrP knock-out mice provided an approach to carry out reverse genetics on PrP, both in regard to prion disease and to its physiological role.
ZR 105
MH Amyloid/genetics; Animals; Brain/metabolism; Gene Expression; Genetic Predisposition to Disease; Human; Mice; Mice, Knockout; Mice, Transgenic; *Models, Animal; Mutation; Phenotype; PrPsc Proteins/genetics; Prion Diseases/*genetics/transmission; Prions/*genetics; Protein Precursors/genetics; Scrapie/genetics; Species Specificity; Spleen/metabolism
AD MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, London, UK
SP englisch
PO England