Source: UNIVERSITY OF WASHINGTON submitted to
STRAIN TYPING OF CHRONIC WASTING DISEASE (CWD) AND SCRAPIE BY INTRACEREBRAL INOCULATION INTO TRANSGENIC AND INBRED MOUSE LINES
Sponsoring Institution
Agricultural Research Service/USDA
Project Status
TERMINATED
Funding Source
Reporting Frequency
Annual
Accession No.
0411895
Grant No.
(N/A)
Project No.
5348-32000-030-01S
Proposal No.
(N/A)
Multistate No.
(N/A)
Program Code
(N/A)
Project Start Date
Sep 28, 2007
Project End Date
Sep 27, 2012
Grant Year
(N/A)
Project Director
KNOWLES JR D P
Recipient Organization
UNIVERSITY OF WASHINGTON
4333 BROOKLYN AVE NE
SEATTLE,WA 98195
Performing Department
COMPARATIVE PATHOLOGY
Non Technical Summary
(N/A)
Animal Health Component
(N/A)
Research Effort Categories
Basic
40%
Applied
20%
Developmental
40%
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
3113310110310%
3113610110360%
3113899110320%
3113410110310%
Goals / Objectives
To identify and differentiate typical and atypical case samples of CWD and Scrapie by characterizing the biologic phenotype and pathologic profile of these agents when administered to susceptible lines of transgenic and inbred mice.
Project Methods
Tissue samples from deer, elk, sheep and goats with Transmissible Spongiform Encephalopathy (TSE) will be administered to mice by intracerebral injection. Multiple tissue types will be included, such as samples of brain, lymph node, blood, urine, feces, antler velvet and muscle. Mouse models used as recipient hosts will include both preexisting and recently created transgenic and inbred mouse lines. Recipient mouse phenotype will be evaluated by measuring clinical response, population disease rate, incubation time, and pathologic profile within the central nervous system (CNS). Pathologic profile of CNS lesion foci is assessed by evaluating anatomic localization, spongiform change, astrocytic gliosis, and deposition of protease resistant prion protein. BSL-1; 9-4-06. Documents SCA with U. of WA.

Progress 09/28/07 to 09/27/12

Outputs
Progress Report Objectives (from AD-416): To identify and differentiate typical and atypical case samples of CWD and Scrapie by characterizing the biologic phenotype and pathologic profile of these agents when administered to susceptible lines of transgenic and inbred mice. Approach (from AD-416): Tissue samples from deer, elk, sheep, and goats with Transmissible Spongiform Encephalopathy (TSE) will be administered to mice by intracerebral injection. Multiple tissue types will be included, such as samples of brain, lymph node, blood, urine, feces, antler velvet, and muscle. Mouse models used as recipient hosts will include both preexisting and recently created transgenic and inbred mouse lines. Recipient mouse phenotype will be evaluated by measuring clinical response, population disease rate, incubation time, and pathologic profile within the central nervous system (CNS). Pathologic profile of CNS lesion foci is assessed by evaluating anatomic localization, spongiform change, astrocytic gliosis, and deposition of protease resistant prion protein. This work relates to sub-objective 1.1 of parent project in proving data supporting improved control and eradication efforts. This is the final report for this SCA which expires in September 2012, which was to identify and differentiate typical and atypical case samples of CWD and scrapie by characterizing the biologic phenotype and pathologic profile of these agents when administered to susceptible lines of transgenic and inbred mice. Mice were inoculated with tissue from sheep with Nor98-like and classical scrapie and from mule deer with chronic wasting disease. Mice are monitored for incubation time and clinical disease, and evaluated postmortem for pathologic changes in the brain and other tissues along with accumulation of abnormal prion within the tissues. In addition, a study was conducted using array-based monitoring of cytokine protein expression in several tissues and serum during the progression of scrapie infection in a transgenic mouse model. These results are relevant to developing biomarkers of scrapie disease as well as determining mechanisms of prion-associated neurologic disease. Project progress was monitored by ADODR, ADRU scientists and University of Washington collaborators through personnel visits, conference calls and electronic exchange of data.

Impacts
(N/A)

Publications


    Progress 10/01/10 to 09/30/11

    Outputs
    Progress Report Objectives (from AD-416) To identify and differentiate typical and atypical case samples of CWD and Scrapie by characterizing the biologic phenotype and pathologic profile of these agents when administered to susceptible lines of transgenic and inbred mice. Approach (from AD-416) Tissue samples from deer, elk, sheep, and goats with Transmissible Spongiform Encephalopathy (TSE) will be administered to mice by intracerebral injection. Multiple tissue types will be included, such as samples of brain, lymph node, blood, urine, feces, antler velvet, and muscle. Mouse models used as recipient hosts will include both preexisting and recently created transgenic and inbred mouse lines. Recipient mouse phenotype will be evaluated by measuring clinical response, population disease rate, incubation time, and pathologic profile within the central nervous system (CNS). Pathologic profile of CNS lesion foci is assessed by evaluating anatomic localization, spongiform change, astrocytic gliosis, and deposition of protease resistant prion protein. During FY2011, collaborative work between ADRU scientists and faculty at the University of Washington was focused on array-based monitoring of cytokine protein expression in several tissues and serum during the progression of scrapie infection in a transgenic mouse model. The results are relevant to developing biomarkers of scrapie disease as well as determine mechanisms of prion-associated neurologic disease. There are regular interactions between the lead scientist, ADRU scientists and University of Washington collaborators through personnel visits, conference calls and electronic exchange of data.

    Impacts
    (N/A)

    Publications


      Progress 10/01/09 to 09/30/10

      Outputs
      Progress Report Objectives (from AD-416) To identify and differentiate typical and atypical case samples of CWD and Scrapie by characterizing the biologic phenotype and pathologic profile of these agents when administered to susceptible lines of transgenic and inbred mice. Approach (from AD-416) Tissue samples from deer, elk, sheep and goats with Transmissible Spongiform Encephalopathy (TSE) will be administered to mice by intracerebral injection. Multiple tissue types will be included, such as samples of brain, lymph node, blood, urine, feces, antler velvet and muscle. Mouse models used as recipient hosts will include both preexisting and recently created transgenic and inbred mouse lines. Recipient mouse phenotype will be evaluated by measuring clinical response, population disease rate, incubation time, and pathologic profile within the central nervous system (CNS). Pathologic profile of CNS lesion foci is assessed by evaluating anatomic localization, spongiform change, astrocytic gliosis, and deposition of protease resistant prion protein. Documents SCA with U. of WA. The purpose of this SCA is to identify and differentiate typical and atypical case samples of Chronic Wasting Disease (CWD) and scrapie by characterizing the biologic phenotype and pathologic profile of these agents when administered to susceptible lines of transgenic and inbred mice. Mice have been inoculated with tissue from sheep with two Nor98- like isolates and classical scrapie, and with tissue from mule deer. Mice are monitored for incubation time and clinical disease, and evaluated postmortem for pathologic changes in the brain and other tissues along with accumulation of abnormal prion within the tissues. There are regular interactions between the ADODR, ADRU scientists and University of Washington collaborators through personnel visits, conference calls and electronic exchange of data.

      Impacts
      (N/A)

      Publications


        Progress 10/01/08 to 09/30/09

        Outputs
        Progress Report Objectives (from AD-416) To identify and differentiate typical and atypical case samples of CWD and Scrapie by characterizing the biologic phenotype and pathologic profile of these agents when administered to susceptible lines of transgenic and inbred mice. Approach (from AD-416) Tissue samples from deer, elk, sheep and goats with Transmissible Spongiform Encephalopathy (TSE) will be administered to mice by intracerebral injection. Multiple tissue types will be included, such as samples of brain, lymph node, blood, urine, feces, antler velvet and muscle. Mouse models used as recipient hosts will include both preexisting and recently created transgenic and inbred mouse lines. Recipient mouse phenotype will be evaluated by measuring clinical response, population disease rate, incubation time, and pathologic profile within the central nervous system (CNS). Pathologic profile of CNS lesion foci is assessed by evaluating anatomic localization, spongiform change, astrocytic gliosis, and deposition of protease resistant prion protein. Documents SCA with U. of WA. Significant Activities that Support Special Target Populations The purpose of this SCA is to identify and differentiate typical and atypical case samples of CWD and scrapie by characterizing the biologic phenotype and pathologic profile of these agents when administered to susceptible lines of transgenic and inbred mice. Mice have been inoculated with tissue from sheep with two Nor98-like isolates and classical scrapie, and with tissue from mule deer. Mice are monitored for incubation time and clinical disease, and evaluated postmortem for pathologic changes in the brain and other tissues along with accumulation of abnormal prion within the tissues. There are regular interactions between the ADODR, ADRU scientists and University of Washington collaborators through personnel visits, conference calls and electronic exchange of data.

        Impacts
        (N/A)

        Publications


          Progress 10/01/07 to 09/30/08

          Outputs
          Progress Report Objectives (from AD-416) To identify and differentiate typical and atypical case samples of CWD and Scrapie by characterizing the biologic phenotype and pathologic profile of these agents when administered to susceptible lines of transgenic and inbred mice. Approach (from AD-416) Tissue samples from deer, elk, sheep and goats with Transmissible Spongiform Encephalopathy (TSE) will be administered to mice by intracerebral injection. Multiple tissue types will be included, such as samples of brain, lymph node, blood, urine, feces, antler velvet and muscle. Mouse models used as recipient hosts will include both preexisting and recently created transgenic and inbred mouse lines. Recipient mouse phenotype will be evaluated by measuring clinical response, population disease rate, incubation time, and pathologic profile within the central nervous system (CNS). Pathologic profile of CNS lesion foci is assessed by evaluating anatomic localization, spongiform change, astrocytic gliosis, and deposition of protease resistant prion protein. Documents SCA with U. of WA. Significant Activities that Support Special Target Populations Strain Typing Of Chronic Wasting Disease (CWD) And Scrapie By Intracerebral Inoculation Into Transgenic And Inbred Mouse Lines. Project number 5348-32000-026-07S. This report serves to document research conducted under a specific cooperative agreement between ARS and the University of Washington. Additional details of research can be found in the report for the parent project 5348-32000-026-00D Transmissible Spongiform Encephalopathies: the role of genetics, strain variation, and environmental contamination in disease control. The purpose of this SCA is to identify and differentiate typical and atypical case samples of CWD and scrapie by characterizing the biologic phenotype and pathologic profile of these agents when administered to susceptible lines of transgenic and inbred mice. Mice have been inoculated with tissue from sheep with Nor98-like and classical scrapie and are monitored for incubation time, clinical disease and postmortem evaluation of disease associated changes in the brain and accumulation of abnormal prions in tissues. There are regular interactions between the ADODR, ADRU scientists and University of Washington collaborators through personnel visits, conference calls and electronic exchange of data.

          Impacts
          (N/A)

          Publications


            Progress 10/01/06 to 09/30/07

            Outputs
            Progress Report Objectives (from AD-416) To identify and differentiate typical and atypical case samples of CWD and Scrapie by characterizing the biologic phenotype and pathologic profile of these agents when administered to susceptible lines of transgenic and inbred mice. Approach (from AD-416) Tissue samples from deer, elk, sheep and goats with Transmissible Spongiform Encephalopathy (TSE) will be administered to mice by intracerebral injection. Multiple tissue types will be included, such as samples of brain, lymph node, blood, urine, feces, antler velvet and muscle. Mouse models used as recipient hosts will include both preexisting and recently created transgenic and inbred mouse lines. Recipient mouse phenotype will be evaluated by measuring clinical response, population disease rate, incubation time, and pathologic profile within the central nervous system (CNS). Pathologic profile of CNS lesion foci is assessed by evaluating anatomic localization, spongiform change, astrocytic gliosis, and deposition of protease resistant prion protein. BSL-1; 9-4-06. Documents SCA with U. of WA. Significant Activities that Support Special Target Populations This report serves to document research conducted under a specific cooperative agreement between ARS and the University of Washington. Additional details of research can be found in the report for the parent project 5348-32000-026-00D Transmissible Spongiform Encephalopathies: the role of genetics, strain variation, and environmental contamination in disease control. The purpose of this new SCA is to identify and differentiate typical and atypical case samples of CWD and scrapie by characterizing the biologic phenotype and pathologic profile of these agents when administered to susceptible lines of transgenic and inbred mice. There will be weekly interactions between the ADODR, ADRU scientists and University of Washington collaborators through personnel visits, conference calls and emails.

            Impacts
            (N/A)

            Publications