Non human primates (NHPs) are essential in the study of genetic factors that influence susceptibility to AIDS, as well as other multifactorial diseases, such as cancer, osteoporosis, hypertension, atherosclerosis and psychological disorders. The ability to control genetic and environmental factors in captive NHP populations provides a powerful means for quantifying the influence of each on risk factors and outcomes of complex diseases. Use of ART will result in the production of completely MHC-defined and genetically identical macaques. The utility of MHC-defined and genetically identical animals in relevant viral challenge models would be enormous and have tremendous specific impact on the ability to assess vaccine efficiency, as well as having tremendous general implications for biomedical research and human health.
In Specific Aim #1, the investigators will use blastomere biopsy and PCR in conjunction with in vitro fertilization (IVF) and selective embryo transfer, to produce approximately 150 MHC-defined offspring over the five year study period.
In Specific Aim #2, they will develop strategies and techniques for the production of pairs or multiple sets of genetically identical monkeys by blastomere separation and will use these techniques to produce sets of age- matched, genetically identical MHC-defined monkeys.
In Specific Aim #3, they will determine the optimal method of oocyte activation for production of developmentally competent rhesus monkey embryos by nuclear transfer, and use markers of nucleolar transcription and totipotency to determine whether incomplete nuclear reprogramming is a common feature of rhesus monkey embryos reconstituted with somatic cell nuclei. These advances will be crucial to the development of cloning technologies in the rhesus macaque. The investigators plan to develop a prototypic animal production program that will be central to the future of the Regional Primate Centers. MHC-defined animals produced using these techniques will complement recent developments in tetramer and ELISPOT technologies in rhesus macaques and provide valuable animals for AIDS vaccine research. Additionally, genetically identical macaques will have general utility in biomedical research, especially to the neuroscience community.
