RESUMEN
TSEs (transmissible spongiform encephalopathies) are neurodegenerative diseases of various mammalian species, the best known of which include BSE (bovine spongiform encephalopathies) in cattle, CJD (Creutzfeldt-Jakob disease) in humans, scrapie in sheep and CWD (chronic wasting disease) in deer. This review examines the emergence of various TSE strains and their transmission, and discusses disease surveillance and control.
Asunto(s)
Síndrome de Creutzfeldt-Jakob/genética , Variación Genética , Enfermedades por Prión/epidemiología , Enfermedades por Prión/transmisión , Síndrome de Creutzfeldt-Jakob/clasificación , Síndrome de Creutzfeldt-Jakob/epidemiología , Humanos , Incidencia , Enfermedades por Prión/clasificación , Enfermedades por Prión/prevención & controlRESUMEN
The PrP gene of the host exerts a major influence over the outcome of transmissible spongiform encephalopathy (TSE) disease, but the mechanism by which this is achieved is not understood. We have introduced a specific mutation into the endogenous murine PrP gene using gene targeting to produce transgenic mice with a single amino acid alteration (proline to leucine) at amino acid position 101 in their PrP protein (P101L). The effect of this alteration on incubation time, targeting and PrP(Sc) formation has been studied in TSE-infected animals. Transgenic mice carrying the P101L mutation in PrP have remarkable differences in incubation time and targeting of central nervous system pathology compared with wild-type littermates, following inoculation with infectivity from human, hamster, sheep and murine sources. This single mutation can alter incubation time across three species barriers in a strain-dependent manner. These findings suggest a critical role for the structurally 'flexible' region of PrP in agent replication and targeting of TSE pathology.