Transmission of Prion Diseases
The new variant of Creutzfeldt-Jacob disease in humans is caused by eating meat infected with bovine spongiform encephalopathy (BSE). The cattle, in turn, were infected from sheep suffering from scrapie. However, no direct transmission from sheep to humans appears to occur. The important question of how prion diseases are passed from one species to another is addressed in the December issue of the Proceedings of the National Academy of Sciences. The genes responsible for transmission of the disease between different species have at least been narrowed down. Michael R. Scott and his colleagues at the University of California have identified which region of a prion is likely responsible for crossing the species barrier. In their study, they used a mouse strain that is very sensitive to BSE. This enabled them to determine the infectivity of bovine tissue before the cattle themselves showed any symptoms of the disease.
The genes for either human or bovine prions were inserted into the genetic material of the mice. Accordingly, the test animals did not produce the normal mouse prion protein, but instead produced the form found in cattle or humans. If the mice with the human prion gene were fed damaged human prions, they showed the characteristic symptoms of the disease. Animals with the bovine gene also responded to disease-causing bovine prions.
The damaged form of prions has a different fold than the normal form. It seems that the disease-causing proteins cause the he althy ones to fold the same way. In order to find out which region of the prion gene is responsible for the external shape, only parts of the mouse prion gene were exchanged with the human or bovine prion gene. A strain of mice with part-human, part-mouse prion genes was found to be susceptible to human prion diseases. But a similar strain with bovine gene regions did not respond to BSE pathogens.
The gene sequence taken from cattle was slightly shorter than that from humans. The researchers assumed that the different sequence must contain the genes that decide whether or not infection takes place across different species. In this way, the region could be narrowed down to four genes.
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