Cre-loxP mediated control of PrP to study transmissible spongiform encephalopathy diseases.
Expression of the PrP glycoprotein is essential for the development of the transmissible spongiform encephalopathy (TSE) or prion diseases. Although PrP is widely expressed in the mouse, the precise relevance of different PrP-expressing cell types to disease remains unclear. To address this, we generated two lines of floxed PrP gene-targeted transgenic mice using the Cre recombinase-loxP system. These floxed mice allow a functional PrP allele to be either switched "on" or "off." We demonstrate control of PrP expression for both alleles following Cre-mediated recombination, as determined by PrP mRNA and protein expression in the brain. Moreover, we show that Cre-mediated alteration of PrP expression in these mice has a major influence on the development of TSE disease. These floxed PrP mice will allow the involvement of PrP expression in specific cell types following TSE infection to be defined, which may identify potential sites for therapeutic intervention.
Tuzi
Nadia L
NL
Institute for Animal Health, Neuropathogenesis Unit, Edinburgh, UK. nadia.tuzi@bbsrc.ac.uk
Clarke
Alan R
AR
Bradford
Barry
B
Aitchison
Lorraine
L
Thomson
Val
V
Manson
Jean C
JC
D000818:Animals; D001483:Base Sequence; D002678:Chimera; D017931:DNA Primers; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D016678:Genome; D006801:Humans; D019426:Integrases / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D017096:Prion Diseases / Q000235:genetics*; D011328:Prions / Q000235:genetics*; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification
D017931:DNA Primers; D016326:Extracellular Matrix Proteins; D011328:Prions; C077112:Lox protein, mouse; D012313:RNA; D008249:Protein-Lysine 6-Oxidase; C045073:Cre recombinase; D019426:Integrases