This Funding Opportunity Announcement (FOA), issued by the National Institute of Mental Health (NIMH), the National Institute on Aging (NIA), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), and the National Institute on Drug Abuse (NIDA), invites Phased Innovation (R21/R33) grant applications from organizations/institutions that propose the development and characterization of novel mouse models that express human genes or human genetic elements that can aid in understanding the molecular mechanisms underlying brain function and the physiological function/significance of gene variants and gene dosage abnormalities that have been identified as possibly being involved in mental disorders, addiction, neurodegenerative disorders of aging, and alcoholism as well as related comorbid conditions.