Transgenetics and gene targeting in studies of prion diseases.

Abstract

Prions cause a group of human and animal neurodegenerative diseases which are now classified together because their etiology and pathogenesis involve modification of the prion protein (PrP) (PRUSINER 1991). Prion diseases are manifest as infectious, genetic, and sporadic disorders (Table 1). These diseases can be transmitted among mammals by the infectious particle designated “prion” (PRUSINER 1982). Despite intensive searches over the past three decades no nucleic acid has been found within prions (ALPER et al. 1966, 1967; HUNTER 1972; RIESNER etal. 1992); however, a modified isoform of the host-encoded designated PrPSc is essential for infectivity (BUELER et al. 1993; PRUSINER 1991; PRUSINER et al. 1983, 1993b,c). In fact, considerable experimental data argue that prions are composed exclusively of PrPSc. Earlier terms used to describe the prion diseases include: transmissible encephalopathies, spongiform encephalopathies, and slow virus diseases (GAJDUSEK 1977, 1985; SIGURDSSON 1954)