YEARS

1999-

AUTHORS

Janine R Wajchman

TITLE

TRANSGENIC MOUSE MODELS FOR RPE TRANSPLANTATION

ABSTRACT

Age-related macular degeneration (AMD) is a leading cause of blindness in the United States. Replacement of damaged cells with healthy retinal cells is a promising approach to the treatment of this, and other, retinal diseases. However, many obstacles must be overcome before transplantation will be clinically feasible. Our goal is to identify the critical immunological problems in RPE transplantation. using transgenic mice. Our first specific aim is to develop a transplant model in which the nominal antigen is defined and one in which rejection can be mediated by T cells from TCR transgenic mice specific for the defined antigen. These transgenic mice have OVA-specific T cells expressing the TCR transgene that is either MHC class I restricted (OT-I) or MHC class II restricted (OT-II). Our intention is to use RPE cells of OVA transgenic mice as donors for transplantation either directly into the TCR transgenic mice or syngeneic B6 mice with adoptive transfer of TCR transgenic cells. Our second specific aim is to produce a transgenic mouse model system that more realistically reflects the situation with AMD. These transgenic mice will be constructed such that the RPE can be ablated prior to transplantation. A construct consisting of the thymidine kinase (TK) gene under the regulation of the tyrosinase-related-protein- 1(TRP-1) promoter will be made. TK produced in pigmented cells with convert a prodrug, ganciclovir, into an active from that will subsequently kill the mammalian cells expressing this gene, thereby providing a more realistic environment or RPE transplantation.

FUNDED PUBLICATIONS

  • Genetic tagging shows increased frequency and longevity of antigen-presenting, skin-derived dendritic cells in vivo.
  • Genetic tagging shows increased frequency and longevity of antigen-presenting, skin-derived dendritic cells in vivo
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    18 TRIPLES      16 PREDICATES      19 URIs      8 LITERALS

    Subject Predicate Object
    1 grants:d76db73a5d7b2b79f288a22604730386 sg:abstract Age-related macular degeneration (AMD) is a leading cause of blindness in the United States. Replacement of damaged cells with healthy retinal cells is a promising approach to the treatment of this, and other, retinal diseases. However, many obstacles must be overcome before transplantation will be clinically feasible. Our goal is to identify the critical immunological problems in RPE transplantation. using transgenic mice. Our first specific aim is to develop a transplant model in which the nominal antigen is defined and one in which rejection can be mediated by T cells from TCR transgenic mice specific for the defined antigen. These transgenic mice have OVA-specific T cells expressing the TCR transgene that is either MHC class I restricted (OT-I) or MHC class II restricted (OT-II). Our intention is to use RPE cells of OVA transgenic mice as donors for transplantation either directly into the TCR transgenic mice or syngeneic B6 mice with adoptive transfer of TCR transgenic cells. Our second specific aim is to produce a transgenic mouse model system that more realistically reflects the situation with AMD. These transgenic mice will be constructed such that the RPE can be ablated prior to transplantation. A construct consisting of the thymidine kinase (TK) gene under the regulation of the tyrosinase-related-protein- 1(TRP-1) promoter will be made. TK produced in pigmented cells with convert a prodrug, ganciclovir, into an active from that will subsequently kill the mammalian cells expressing this gene, thereby providing a more realistic environment or RPE transplantation.
    2 sg:fundingAmount 79512.0
    3 sg:fundingCurrency USD
    4 sg:hasContribution contributions:568a5b4a96227bfbaa43f8937deab68c
    5 sg:hasFieldOfResearchCode anzsrc-for:11
    6 anzsrc-for:1107
    7 sg:hasFundedPublication articles:046a5ac8f26791afc715697ef1a119e3
    8 articles:a062956ac50b0fddee1a2f49ee6f66db
    9 sg:hasFundingOrganization grid-institutes:grid.280030.9
    10 sg:hasRecipientOrganization grid-institutes:grid.189967.8
    11 sg:language English
    12 sg:license http://scigraph.springernature.com/explorer/license/
    13 sg:scigraphId d76db73a5d7b2b79f288a22604730386
    14 sg:startYear 1999
    15 sg:title TRANSGENIC MOUSE MODELS FOR RPE TRANSPLANTATION
    16 sg:webpage http://projectreporter.nih.gov/project_info_description.cfm?aid=6384558
    17 rdf:type sg:Grant
    18 rdfs:label Grant: TRANSGENIC MOUSE MODELS FOR RPE TRANSPLANTATION
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