Systematic and scalable phenotyping of mouse mutants for neuropsychiatric disease genetics

PROJECT SUMMARY/ABSTRACT In the past decade, significant progress has been made in identifying genetic variants associated with neurodevelopmental and psychiatric disorders like autism, schizophrenia, and intellectual disability. However, understanding how these genes affect brain function and contribute to disease remains a challenge due to the diverse experimental approaches used. To address this, we have assembled the Washington University Scalable Mouse Assay Center (WU-SMAC), an Assay and Data Generation Center (ADGC) for the SSPsyGene consortium. We will comprehensively investigate the impact of prioritized mutations known to cause neurodevelopmental and psychiatric disorders using over 100 mouse lines. Through a combination of behavioral analysis, anatomical mapping, and molecular assessments, our project seeks to uncover the molecular and spatial changes in the brain caused by these mutations and their subsequent effects on behavior. We will deeply assess the phenotype of each mutant using high-content, machine-learning driven behavioral analysis, automated home-cage monitoring of learning behavior and cognitive flexibility, and careful single nucleus & spatial transcriptomics. We will coordinate data serving and distribution with the other ADGCs and Data Resource and Administrative Coordination Center, and provide a unique mouse neuropsychiatric disease brain bank for the entire consortium to enable the replication of findings from other ADGC's systems within the complex milieu of a fully developed mammalian brain.