(PRECLINICAL MODELS CORE (PMC): CORE F)  PROJECT SUMMARY Description: The Preclinical Models Core (PMC) supports IDDRC users who seek new treatments for IDD by studying these disorders in 3 kinds of preclinical models: (1) Rodent models: This Core component characterizes behaviors in mouse models of genetic or acquired disabilities. Measured behaviors include learning, memory, social preference, ultrasonic vocalization, sleep and anxiety. (2) Stem cell models: This Core component assists users to create disease models by generating induced pluripotent stem cells (iPSCs) using standard reprogramming technologies or by genome editing, such as CRISPR-Cas, on established iPSC lines. These cells, some derived from humans with IDD, afford a model in which to scrutinize cellular consequences of genetic disease and to evaluate the efficacy of possible therapies. (3) Tissue culture models: This Core component supports users to generate tissue culture models in which to study the development and behavior of enriched or mixed populations of primary brain cells, including neurons, astrocytes, oligodendroglia, microglia and endothelia. These cells originate in genetically manipulated rodents or they are normal cells exposed to environmental stimuli, including drugs and toxins. The Tissue Culture Service and Stem Cell Service interact closely, since they share several in vitro methodologies and serve as a conduit to drive and help design rodent behavior testing. The PMC emphasizes training of users and their staff. Trained users can continue studies in their own laboratory or they can utilize the equipment in the PMC at reduced cost. This core interacts with others in the Center. It will exchange protocols, services and best practices with other IDDRCs in the Network. Relevance to IDDRC Mission: The PMC bridges all three domains of “Genes, Brain, and Behavior”, the theme of the CHOP/Penn IDDRC (see Overall: Overview of Center). The Core was developed in response to a user survey (2014) that emphasized a need for an IDD-focused facility for the study of mammalian behavior and one to address the potential of current stem cell technologies, including CRISPR-Cas. Eligibility: These services are available both to approved users of the IDDRC at CHOP/UPenn and to users at other Centers in the Network.