PILOT PROJECT ON GENETIC DISEASES IN NON-HUMAN PRIMATES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a pilot project to test the hypothesis that the high frequency of failure to thrive and early death among primates in closed colonies bred in this country is, in part, due to recessively inherited metabolic diseases. Because of the obligatory inbreeding present in closed colonies of relatively small size and the high probability that founding animals carry a number of gene mutations at loci important in the thousands of steps in intermediary metabolism and other cell and organ functions, it is likely that this hypothesis is correct. In the pilot project, the Referral Center provided consultation for scientists in charge of primate colonies at the New England Regional Primate Research Center and the South Alabama University School of Medicine and provided access to the Center's experienced metabolic laboratory for metabolic screening of primates with failure to thrive and other signs of metabolic disease. In the initial phase of this project, normal age related standards for urinary and serum levels of amino acids, organic acids, carbohydrates, and glycosaminoglycans were determined in the species of interest. This phase has been completed. In the next phase to be expanded to an NCRR-supported primate colony, animals exhibiting signs that may be indicative of metabolic disease, including unexplained failure to thrive, dysmorphia, neurologic and behavioral abnormalities, seizures, vomiting, metabolic acidosis, growth retardation, cataracts, and bony deformities, will be screened for the presence of abnormal metabolites in urine and blood. Animals with abnormalities will be further studied by appropriate biochemical and molecular methods to determine the nature of the underlying genetic defect. Disorders that offer new and important models for biomedical research on disease pathogenesis and therapy will be further studied and the Referral Center will assist the scientists in charge of these colonies in establishing breeding lines of carrier animals. During the period since this pilot study began we have received urine samples from monkeys of the species indicated: Rhesus (80), Marmosets (8), Squirrel monkeys of 3 subspecies (42 Bolivian, 18 Peruvian, 12 Guayanese). These animals were chosen by the collaborating institution as healthy controls. Samples were studied to determine semi-quantitative distribution of amino acids, organic acids and carbohydrates using paper chromatographic methods that are cheap and have been shown to be reasonably effective in detecting abnormal metabolites in dog and cat urine. In addition, 15 samples were examined by gas chromatography and HPLC to verify the semi-quantitative findings. No striking abnormalities based on human and dog standards were seen and there were no obvious differences between the primate species. The concentration of branched chain amino acids in the urine of the two primate species studied appears to be lower than that in human urine. We now have a baseline study set that should provide the basis for studies in animals with clinical signs of illness suggestive of metabolic disease.