Humanized prion protein knock-in by Cre-induced site-specific recombination in the mouse.

To establish humanized mice with a knock-in (gene replacement) technique, we constructed a targeting vector which consists of the human prion protein and the loxP sequences. The introduced human prion protein with the loxP system in the embryonic stem cells was transmitted through the mouse germ line. Transient expression of Cre recombinase in the fertilized eggs resulted in the prion protein humanized mice. The Cre-loxP-mediated gene replacement is a simple and efficient method which is generally applicable to make humanized animal models.