The primary goal of the Transgenic Huntington's Disease Monkey Resource (THDMR) parent R24 grant is to generate transgenic Huntington's disease nonhuman primates (HD monkeys) with essential characterization that readies them for preclinical research. Specifically, a series of memory tasks, emotional tests, and social interaction will be used to characterize the HD monkeys, which will provide investigators a cognitive and behavioral profile baseline of the animals on which to assess the effectiveness of their preclinical treatments. The automated equipment requested in this revision grant will not only facilitate, but will enhance this characterization and allow for expansion into metabolic profiling and more complex social behaviors of HD monkeys. The expansion into examining metabolic profiles is important, because weight loss and metabolic dysfunction is a hallmark symptom of HD in humans. Therefore, purchasing a large run housing cage will allow us to socially house the HD monkeys providing a richer, complex profile of their social behavior, in contrast to what can be obtained with dyadic social interactions. The installation of radiofrequency tracking and video systems will enable the 24hr/7day/week monitoring of the animals social interaction, as well as energy expenditure, potential sleep disturbances and better characterization of motor problems. In addition, automated feeding systems accurately measure food intake of individual animals, which provides an indication of energy intake and could alert research and veterinary staff to animals with inappetence that may need medical attention. Lastly, the addition of a dual energy X-ray absorptiometry (DEXA) scanner will provide precise measures of fat and lean body mass, which have been shown to be dysregulated in HD patients. Overall, the installation and implementation of the automated equipment will streamline data collection, enhancing our ability to characterize HD monkey disease progression, as well as expedite the evaluation of effective preclinical treatments.
Transgenic Huntington's disease (HD) monkeys, sponsored by the ORIP, recapitulate disease progression and develop clinical features similar to human HD patients. In order to facilitate the preclinical application of the HD monkey model, a Transgenic Huntington's Disease Monkey Resource (THDMR) was established to produce HD monkeys with essential characterization that readies them for preclinical research. The automated equipment requested in this revision will enhance and expand on the characterization of HD monkeys, and will be made available to preclinical investigators to streamline the evaluation of effectiveness of preclinical treatments.
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