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Cre‐loxP mediated control of PrP to study transmissible spongiform encephalopathy diseases
Author(s) -
Tuzi Nadia L.,
Clarke Alan R.,
Bradford Barry,
Aitchison Lorraine,
Thomson Val,
Manson Jean C.
Publication year - 2004
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/gene.20046
Subject(s) - cre recombinase , cre lox recombination , biology , transgene , genetically modified mouse , transmissible spongiform encephalopathy , allele , recombinase , bovine spongiform encephalopathy , gene , virology , disease , scrapie , prion protein , genetics , medicine , pathology , recombination
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. genesis 40:1–6, 2004. © 2004 Wiley‐Liss, Inc.