U.S. flagAn official website of the United States government
                    Here's how you know **Official websites use .gov**
                            
                            A **.gov** website belongs to an official government organization in the United States.
 **Secure .gov websites use HTTPS**
                            
                            A **lock** (                            
                              A locked padlock                                                      
                            
                            ) or **https://** means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.


Menu Agricultural Research Service
						
                    U.S. DEPARTMENT OF AGRICULTURE
 Virus and Prion Research: Ames, IA
 close



    Research

                    Research Projects
                                    Publications
                                    Collaborations
                                    News
                People

                    Staff Listing
                                    CareersSearch small
                    Search
            
            ARS Home
                                About ARS
                                Contact Us




ARS Home Midwest Area Ames, Iowa National Animal Disease Center Virus and Prion Research Research Publications at this Location





- ARS National Programs
- Search for a scientific manuscript
- Search for a research project
- ARS Software
- Programs and Projects
- Collaborations
- Subjects of Investigation
- Publications

Title:   Author  item
                                            Kunkle, Robertitem
                                            Hamir, Amiraliitem
                                            Richt, Juergenitem
                                            Greenlee, Justinitem
                                            Nicholson, Ericitem
                                            Kehrli Jr, Marcus
  Submitted to: Meeting Abstract
                                    Publication Type: Abstract Only
                                    Publication Acceptance Date: 6/12/2008
                                    Publication  Date: 10/8/2008
                                    Citation: Kunkle, R.A., Hamir, A.N., Richt, J.A., Greenlee, J.J., Nicholson, E.M., Kehrli, Jr., M.E. 2008. Lack of Prion Accumulation in Lymphoid Tissues of Scrapie-Affected Sheep with AA136, QR171 Polymorphism Type [abtract]. Prion 2008. p. 75.Interpretive Summary:
                                Technical Abstract: Background:  Sheep scrapie is a transmissible spongiform encephalopathy which can be transmitted horizontally through the shedding of an infectious conformer (PrP**Sc) of the normal cellular prion protein (PrP**c).  Genetics profoundly influence the susceptibility of sheep to scrapie.  PrP**c amino-acid polymorphisms A136V, R154H, Q171R, and Q171H are predictive for relative susceptibility (V136, R154, Q171) or resistance (A136, H154, R171) to classical scrapie in natural settings and in experimental oral inoculation studies.
Objectives:   To compare the clinical course and PrP**Sc tissue distribution in sheep with high resistance and high susceptibility genotypes after inoculation of scrapie-affected sheep brain homogenate directly into the brain.
Methods:  Five sheep each of genotype VRQ/VRQ, ARQ/ARQ(H), VRQ/ARQ, or ARQ/ARR were inoculated via intra-cerebral route with a 10% brain homogenate derived from a ARQ/ARQ sheep affected with scrapie.  Sheep were euthanized in the terminal phase of scrapie development.  Tissues collected at necropsy were examined by light microscopy, immunohistochemistry (IHC) and Western blot.
Results:  All inoculated sheep succumbed to scrapie.  Clinical signs, microscopic lesions, and Western blot profiles were uniform across genotypes and consistent with manifestations of classical scrapie. Mean survival time differences were associated with the 171 polymorphic site with VRQ/VRQ and ARQ/ARQ sheep surviving 18 and 19 months, whereas VRQ/ARR and ARQ/ARR survived 56 and 60 months, respectively.  Labeling of PrP**Sc by IHC revealed similar accumulations in central nervous system tissues across genotypes; however the few PrP**Sc – negative retinas were from QR171 sheep.  Labeling of PrP**Sc in lymphoid tissue was consistently abundant in VRQ/VRQ, present in 4/5 ARQ/ARQ and VRQ/ARR, and totally absent in ARQ/ARR sheep.
Discussion:  The results of the study demonstrate the susceptibility of sheep with the high resistance genotype ARQ/ARR to scrapie by the intra-cerebral inoculation route, with attendant PrP**Sc accumulation in CNS tissues, and concurrent lack of PrP**Sc in lymphoid tissue.  Genetic resistance to scrapie is associated with failure of PrP**Sc to accumulate in lymphoid tissue, and not associated with permissiveness of CNS tissue to PrP**Sc amplification.


Return to top


Connect with ARS Sign up


ARS Home
                            USDA.gov
                            Plain Writing
                            Policies & Links
                            Civil Rights Statements
                            FOIA
                            Accessibility Statement
                            Privacy Policy
                            Non-Discrimination Statement
                            Quality of Information
                            USA.gov
                            WhiteHouse.gov