THIS IS A SHANNON AWARD PROVIDING PARTIAL SUPPORT FOR THE RESEARCH PROJECTS THAT FALL SHORT OF THE ASSIGNED INSTITUTE'S FUNDING RANGE BUT ARE IN THE MARGIN OF EXCELLENCE. THE SHANNON AWARD IS INTENDED TO PROVIDE SUPPORT TO TEST THE FEASIBILITY OF THE APPROACH; DEVELOP FURTHER TESTS AND REFINE RESEARCH TECHNIQUES; PERFORM SECONDARY ANALYSIS OF AVAILABLE DATA SETS; OR CONDUCT DISCRETE PROJECTS THAT CAN DEMONSTRATE THE PI'S RESEARCH CAPABILITIES OR LEAD ADDITIONAL WEIGHT TO AN ALREADY MERITORIOUS APPLICATION. THE APPLICATION BELOW IS TAKEN FROM THE ORIGINAL DOCUMENT SUBMITTED BY THE PRINCIPAL INVESTIGATOR. The ability to produce genetically identical animals for use as models for biomedical research will result in significant cost reductions for research involving both human and animal health. Accurate studies of interactions between genotype and environment are possible when using identical animals. Even more important, far fewer animals are required for experimentation to become statistically valid. Genetically identical animals also allow for experimentation that is otherwise impossible; for instance animals with identical majorhisto-compatibility complexes (MHC) can be utilized in tissue transplantation studies or gene therapy, where cells are collected from one animal and genetically engineered, then transferred into another. Nuclear transplantation is a potential method for producing genetically identical animals. Progress in this area of research has been very encouraging and genetically identical sheep, cattle, and pigs have been produced. Identical rabbits and mice have also been produced by nuclear transplantation, however, research with laboratory species is very limited. Laboratory animals represent the primary animal resource for biomedical research, therefore a great need exists to develop methods for producing genetically identical animals of different laboratory species. The long term goal and overall objective of the proposed research is to develop nuclear transplantation procedures for the production of genetically identical cats. Assisted reproductive technologies including embryo collection and transfer, in vitro fertilization and in vitro embryo culture are well established in the cat making it an ideal target species for studies involving nuclear transplantation. Moreover, cats are extensively used a& investigative models in neuroanatomy, neurosurgery, neurology, neurophysiology, toxicology, reproductive physiology, cardiovascular physiology, and cancer; and in more recent times have become a very important model for studies involving human AIDS. The specific aims of the proposed work involve the adaption of nuclear transplantation techniques already proven effective for the production of genetically identical offspring in other species. Blastomeres collected from embryos at different stages of development will be tested for their ability to serve as nucleus donors for transplantation into enucleated oocytes. The effect of oocyte age on the ability of oocytes to serve as recipient ova for nuclear transplantation will be tested. Oocytes matured in vitro and in vivo will be compared for their ability to serve as recipient ova for nuclear transplantation. Embryos produced in vitro and in vivo will be compared, as will frozen/thawed and fresh embryos for their ability to serve as nucleus donors for nuclear transplantation. Finally, embryos produced by nuclear transplantation will be transferred into recipient females, then pregnancy rates and the percentage of embryos that result in live offspring will be compared to that of normal embryos.