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Title:   Author  item
                                            VARGAS, FRANCISCO - Universidad Centroccidental Lisandro Alvaradoitem
                                            KUROIWA, YOSHIMI - Hematech, Incitem
                                            Greenlee, Justinitem
                                            Hamir, Amiraliitem
                                            Kunkle, Robertitem
                                            KANGAS, TRACY - Iowa Retina Consultantsitem
                                            KANTHASAMY, ANUMANTHA - Iowa State Universityitem
                                            ROBL, JAMES - Hematech, Incitem
                                            Richt, Juergen
  Submitted to: Abstracts World Buiatrics Congress
                                    Publication Type: Abstract Only
                                    Publication Acceptance Date: 9/13/2010
                                    Publication  Date: 11/14/2010
                                    Citation: Vargas, F., Kuroiwa, Y., Hamir, A.N., Greenlee, J.J., Kunkle, R.A., Kangas, T., Kanthasamy, A., Robl, J., Richt, J. A. 2010. Clinical features in prion protein-deficient and wild-type cattle inoculated with transmissible mink encephalopathy (TME) [abstract]. XXVI World Buiatrics Congress 2010, November 14-18, 2010, Santiago, Chile. Available: http://www.kenes.com/buiatrics/cd/pdf/780.pdf.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. Recently, we have reported the generation and characterization of PrP**C-deficient cattle (PrP-/-) produced by a sequential gene targeting system and also we reported that PrP-/-cattle are resistant to prion diseases.
  Objectives: In this study, we wanted to show the clinical features observed in prion protein-deficient and wild-type cattle inoculated with transmissible mink encephalopathy. 
  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. All PRNP-/- and PRNP+/+ calves were further given an extensive clinical examination at the start of the experiment and each 3 months after inoculation with special emphasis in neurological examination. Additionally, the clinical assessment also included electrocardiography (EKG) and ophhtalmoscopic examination. All animals were monitored daily during the experiment.
  Results: All five PRNP+/+ cattle inoculated with TME were euthanized with clinical signs within 18 MPI and contained abnormal PrP**d in their CNS tissues. The most important clinical signs observed in the wild type inoculated group were: low body condition score, low response to cutaneous reflex, lordosis, hyperreaction to stimulations (menace, sounds and light), hypersensitivity in the head; abnormal attitudes and movements (excessive licking, movements of ears and teeth grinding), slow response to pupilar reflex; head lowered, hypersensitivity in the trunk and locomotion alteration. Retinal examination revealed, neovascularization in the optic disc (NVD) and atrophy in the retinal pigment epithelium (RPE). All five PRNP-/- cattle inoculated intracerebrally with a cattle-adapted TME isolate and normal brain homogenate are clinically normal at 36 MPI. However, some PRNP-/- cattle inoculated with TME and normal brain showed mild reaction to some stimulation from the beginning of the experiment. 
  Conclusion: PRNP+/+ wild type inoculated with TME showed nervous clinical signs similar to BSE at 18 MPI.  PRNP-/- inoculated with TME did not develop clinical signs consistent with prion disease. Mild reaction to stimulation observed in some PRNP-/- (inoculated with TME and normal brain) may be associated with alteration of Purkinje cells degeneration.


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