The purpose of the Animal and Antibody Core is to provide animals and antibodies to all components of this Program Project. This includes: 1) Purchase and maintenance of non-human primates;2) Production, quality control and maintenance of MGH MHC inbred miniature swine including the MGH GalT-KO swine;3) The purchase and maintenance of scid and transgenic mice (Projects 3 and 5) including barrier housing;and 4) Production, phenotyping and characterization of murine monoclonal antibodies reactive with swine and baboon cell surface antigens. The Core will provide support for the purchase, housing and care of the nonhuman primates, which will be utilized in all five projects. This Core will provide the facilities, management and technical expertise necessary to produce GalT-KO swine and genetically typed inbred miniature swine for the delivery of organs, blood and tissues to all five projects. The herd is maintained and monitored with the use of a computer database written by the P.I., who will coordinate the breeding, quality control, allocation, transportation and utilization of animals in each Project. Most of the large animals will be committed to Projects 1 and 2, which deal predominantly with large animal xenotransplantation. However, blood and tissues from the non-human primates in Projects 1 and 2 will also be utilized for the studies of transmission of infectious agents and thromboregulation in Projects 4 and 5, respectively. Likewise, pig tissues from animals in Projects 1 and 2 will be provided to Projects 3, 4 and 5 as required. This strategy was adopted to limit the number of animals, conserve resources, and lower costs. The core will also continue an ongoing effort to produce, phenotype and biochemically characterize a large, existing panel of murine monoclonal antibodies (Mabs) reactive with swine and baboon stromal and lymphocyte populations. These Mabs will allow improved characterization of swine cell lineages reconstituting baboon recipients (Projects 1 and 2), and of engrafted pig thymic tissues (Projects 1 and 3). These Mabs will assist in defining the molecular interactions critical to endothelial thromboregulation and transmission of infectious agents (Projects 4 and 5). In addition, T cell-specific Mabs conjugated to diphtheria toxin will be used to deplete lymphocyte populations in baboons as part of the recipient conditioning regimens in Projects 1 and 2. The success of each component of this program will be dependent on the quality, predictability, and accessibility of the animals and antibodies provided by this Core.
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