ANIMAL PHENOTYPING CORE

PROJECT SUMMARY/ABSTRACT – ANIMAL PHENOTYPING Phenotyping animal models of disease is a critical element in our Center’s goal to understand, effectively treat, and when possible, prevent intellectual and developmental disabilities in children. Accordingly, the mission of the Animal Phenotyping Core (Core E, AP) is to assist investigators seeking to discover behavioral, physiological, structural and metabolic phenotypes in diverse rodent models of intellectual and developmental disabilities. The AP Core performs studies primarily in mice and rats to identify the functional alterations resulting from genetic, developmental or environmental manipulations that may impair neural and behavioral development. These include changes in developmental milestones, sensorimotor function, cognitive function, affective and social behaviors, feeding and activity patterns, body composition and/or energy expenditure, patterns of brain activity and anatomy as assessed by brain imaging in MRI/DTI (diffusion tensor imaging) and PET scans. The AP Core accomplishes its goals through SubCores focused on (1) behavior, (2) metabolism, and (3) brain imaging. By combining existing capabilities and highly experienced faculty we have established an animal phenotyping facility uniquely suited to plan, perform and evaluate coordinated behavioral, metabolic, and functional neuroimaging assessments in developing and adult rodents. Through close collaborative efforts with the Neural Cell Engineering and Imaging (NCEI) Core and the Human Clinical Phenotyping (HCP) Core, as well as the Neurogenomics (NGEN) Core, the consequences of defined genetic, environmental and/or physiological alterations are thoroughly characterized to determine their impact in the context of measures most relevant and translatable to the human disease phenotype. The AP Core also makes critical contributions to Aim 2 of the RFK IDDRC signature research project focused on links between mutations in KDM5C and IDD. In addition to the wide range of expertise of its leadership and the resources they bring to this effort, the AP Core also emphasizes the importance of integration across measurement and analytical capabilities, i.e., it facilitates a combination of methodological approaches such as pursuit of brain imaging simultaneously with behavioral studies. We also emphasize, when possible, phenotyping techniques that are most comparable to those used in children with IDD. In pursuit of these scientific objectives, the AP Core leadership, in concert with ADM Core oversight, also carefully monitors IDDRC investigator Core access and user satisfaction, cost effectiveness and quality control.