(CORE F – PMC: PRECLINICAL MODELS CORE) PROJECT SUMMARY Description: The Preclinical Models Core (PMC) supports IDDRC users who study IDD pathophysiology and/or seek new treatments for IDD using one or both of the following preclinical models: (1) Rodent models: This Core component assists users with the characterization of behavioral phenotypes in mouse models of genetic or acquired disabilities. Major behavioral domains assessed in this core include: learning, memory, social preference, communication, motor function, and affective disorder-related behaviors; (2) Human iPSC models: This Core component assists users to create cell models of IDD by generating induced pluripotent stem cells (iPSCs) using standard reprogramming technologies or by genome editing via CRISPR-Cas9 on established iPSC lines, followed by differentiation into neural cell types of interest for molecular and cellular phenotype characterization. These cells, some derived from humans with IDDs, provide a model in which it is possible to scrutinize molecular and cellular consequences of genetic disease and to evaluate the efficacy of possible therapies. The complementary model systems are being used by many of the center investigators, and the two services interact closely under one leadership. The PMC emphasizes training of users and their staff. Trained users can continue studies in their own laboratory, or they can utilize the equipment and/or reagents in the PMC at reduced cost. The services offered by the PMC are complementary to those offered by all of the other center cores, and users frequently use more than one core to complete a project. In addition, the PMC interacts closely with similar cores at sister IDDRCs to share protocols, cross-validate outcome measures, in order to improve rigor and reproducibility across the IDDRC network. Relevance to IDDRC Mission: The PMC bridges all three domains of “Genes, Brain, and Behavior”, the theme of the CHOP/Penn IDDRC (see Research Plan Overall). The Core was developed in response to a user survey in 2014 that emphasized a need for an IDD-focused facility to study IDD-related behavioral and cellular phenotypes in the context of IDD clinical symptoms and to take advantage of the iPSC potentials to gain insights into disease pathophysiology and improve treatment for IDDs in a collaborative manner with other Cores of this IDDRC. Eligibility: These services are available both to approved users of the IDDRC at CHOP/Penn and to users at other Centers in the Network.