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United States Department of Agriculture

Agricultural Research Service

Title: Knocked-out and still walking: prion protein-deficient cattle are resistant to prion disease)

item Richt, Juergen
item Hamir, Amirali
item Kuroiwa, Yoshimi
item Vargas, Francisco
item Kunkle, Robert
item Schonenbrucher, Holger
item Kanthasamy, Anumantha
item Robl, James

Submitted to: Meeting Abstract
Publication Type: Abstract only
Publication Acceptance Date: 8/22/2008
Publication Date: 8/22/2008
Publication URL:
Citation: Richt, J.A., Hamir, A.N., Kuroiwa, Y., Vargas, F., Kunkle, R.A., Schonenbrucher, H., Kanthasamy, A., Robl, J.E. 2008. Knocked-out and still walking: prion protein-deficient cattle are resistant to prion disease [abstract]. Rocky Mountain Prion Research Symposium. Paper No. 10.

Interpretive Summary:

Technical Abstract: Background: Transmissible spongiform encephalopathies (TSEs) or prion diseases are caused by the propagation of a misfolded form (PrP**d) of the normal cellular prion protein, PrP**c. Disruption of PrP**c expression in the mouse results in resistance to PrP-propagation and disease. However, the impact of the ablation of PrP**c function in a natural host species of prion diseases is unknown. Recently, we have reported the generation and characterization of PrP**c deficient cattle (PrP-/-) produced by a sequential gene targeting system. Objectives: In this study we wanted to determine whether PrP-/- cattle are susceptible or resistant to prion diseases. Methods: Five PRNP+/+ wild-type and five PRNP-/- cattle were inoculated intracerebrally with a 10% brain homogenate derived from a bovine infected with a cattle-adapted TME isolate. Six other cattle (three each PRNP+/+ and PRNP-/-) were inoculated with normal brain material. Results: PRNP-/- cattle inoculated intracerebrally with a cattle-adapted transmissible mink encephalopathy (TME) isolate (i) do not replicate abnormal PrP**d in their central nervous system (CNS) for at least 23 months post inoculation (MPI) and (ii) are clinically normal at least 27 MPI. In contrast, all five PRNP+/+ cattle inoculated with TME were euthanized with clinical signs within 18 MPI and contained abnormal PrP**d in their CNS tissues. Discussion: Our results for the first time determine that PrP**c is a critical component in the pathogenesis of TSE disease of a natural host.

Last Modified: 8/24/2016
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