ABSTRACT
Point mutations of the human prion protein (PrP) gene can lead to familial forms of prion diseases, such as Creuzfeldt-Jakob’s disease, Gerstmann-Straussler-Scheinker syndrome, and fatal familial insomnia (FFI). The PrP gene is expressed at high levels in neuronal cells of the adult brain, and in astrocytes and oligodendrocytes. Lower levels of PrP messenger ribonucleic acid (mRNA) have been detected in the heart, lung, and spleen. PrP mRNA has also been detected during mouse embryogenesis in the extraembryonic tissue and in the developing central and peripheral nervous system. The aim of the generation of PrP-null mice was twofold: to address the question of the normal function of PrP, and to test the hypothesis that mice devoid of PrP should be resistant to scrapie pathogenesis after infection with mouse scrapie prions. Positron emission tomography showed that the main neurological feature in FFI is the loss of neurons and astrogliosis in the thalamus, particularly in the medio-dorsal and anterio-ventral thalamic nuclei.
