Developmental expression of PrP in the post-implantation embryo.

Since prion protein (PrP) mRNA and PrP(C) expression levels in transgenic (Tg) mice using the CosSHa.tet vector correlate well with the PrP transgene copy, we constructed Prnp-LacZ Tg animals expressing beta-galactosidase that was inserted into the CosSHa.tet vector. The CosSHa.tet vector was created from a large PrP cosmid clone in which the PrP open reading frame was deleted. In the developing nervous system, the beta-galactosidase marker was not expressed in the neural progenitors of the mitotically active ventricular zone. It is first expressed in cells that have ceased proliferating, migrated radially from the ventricular zone, and differentiated into neurons in the intermediate layer. At E11.5 p.c., motor neurons in the ventral neural tube clearly express the marker transgene. Expression in dorsal neural tube neurons is observed at later stages, after their differentiation. These results indicate that Prnp gene expression in the nervous system begins in post-mitotic neural cells that have undergone neuronal differentiation. This pattern of Prnp expression in the nervous system appears to persist throughout the adult life of mammals.