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Cross-species transmission of prion disease: A study of factors influencing incubation periods in mice
Edward R. Winstead

Creutzfeldt-Jakob disease, a human variant of mad cow disease, and other prion diseases develop at different rates and tend to have long incubation periods. Variation in incubation periods among humans, mice, and sheep has been associated with polymorphisms in the prion protein gene. Other factors in the genome, including polymorphisms in multiple genes, may influence incubation periods, according to two recent studies.

Last month British researchers identified three regions of the mouse genome associated with incubation periods for prion diseases. Now, another team of British researchers expands the list of chromosomal regions linked to prion diseases in mice and says that environmental factors also play a role.

Ian J. Jackson, of the Western General Hospital, in Edinburgh, and colleagues mapped genetic effects on the incubation period to four mouse chromosomes—2, 4, 8, and 15. Incubation periods were also affected by non-genetic factors, including the age of the host's mother and the age of the host at the time of infection. For instance, mice infected later in life had shorter incubation periods than mice infected early in life.

"We found that both genetic and environmental factors are modifying the incubation period in mice," says Jackson. "Finding specific genes that underlie these effects is going to be a tough job because the genetic effects were fairly weak."

The researchers bred two strains of mice that differed in their incubation periods by 100 days. The mouse offspring were infected with tissue from cattle that had bovine spongiform encephalopathy, also known as mad cow disease, and the researchers determined the incubation periods for the infected mice.

The experimental transmission of disease agents between species is known to increase the incubation period and likely to give a different outcome than infection between members of the same species, says Jackson. He notes that prion researchers are interested in this cross-species transmission because of the likelihood that humans developed variant Creutzfeldt-Jakob disease from eating meat from infected cattle. The study appears in Proceedings of the National Academy of Sciences.

The chromosome regions reported by Jackson's group differ from those identified last month by Elizabeth M. C. Fisher, of the Imperial College School of Medicine at St Mary's, London, and colleagues.

See related GNN article
»Beyond polymorphisms: Genome scans and prion disease in mice.

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Manolakou, K. et al. Genetic and environmental factors modify bovine spongiform encephalopathy incubation period in mice. Proc Natl Acad Sci USA 98, 7402-7407 (June 19, 2001).

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