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United States Department of Agriculture

Agricultural Research Service

Title: Production of cattle lacking prion protein)

Author
item Richt, Juergen
item Kasinathan, Poothappillai
item Hamir, Amirali
item Castilla, Joaquin
item Sathiyaseelan, Thillai
item Vargas, Francisco
item Sathiyaseelan, Janaki
item Wu, Hua
item Matsushita, Hiroaki
item Koster, Julie
item Kato, Shinichiro
item Ishida, Isao
item Soto, Claudio
item Robl, James
item Kuroiwa, Yoshimi

Submitted to: Nature Biotechnology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 10/27/2006
Publication Date: 1/1/2007
Citation: Richt, J.A., Kasinathan, P., Hamir, A.N., Castilla, J., Sathiyaseelan, T., Vargas, F., Sathiyaseelan, J., Wu, H., Matsushita, H., Koster, J., Kato, S., Ishida, I., Soto, C., Robl, J.M., Kuroiwa, Y. 2007. Production of cattle lacking prion protein. Nature Biotechnology. 25(1):132-138.

Interpretive Summary: This manuscript describes the successful production of healthy calves that are missing both copies of the prion gene and shows conclusive evidence for functional inactivation of the gene. These calves should be useful for the evaluation of the function of the normal prion protein in cells, the function of the misfolded, infectious form of prion protein in BSE and, potentially, as a source of prion-free bovine products for food and medicine. This work is of broad general interest because of the considerable health and economic impact of BSE in the world.

Technical Abstract: Prion diseases are caused by propagation of misfolded forms of the normal cellular prion protein PrP**C, such as PrP**BSE in bovine spongiform encephalopathy (BSE) in cattle and PrP**CJD in Creutzfeldt-Jakob disease (CJD) in humans. Disruption of PrP**C expression in mice, a species that does not naturally contract prion diseases, results in no apparent developmental abnormalities. However, the impact of ablating PrP**C function in natural host species of prion diseases is unknown. Here we report the generation and characterization of PrP**C-deficient cattle produced by a sequential gene-targeting system. At over 20 months of age, the cattle are clinically, physiologically, histopathologically, immunologically and reproductively normal. Brain tissue homogenates are resistant to prion propagation in vitro as assessed by protein misfolding cyclic amplification. PrP**C-deficient cattle may be a useful model for prion research and could provide industrial bovine products free of prion proteins.

Last Modified: 8/24/2016
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