PT - JOURNAL ARTICLE AU - Nicholas P. Boyer AU - Caroline Monkiewicz AU - Shalini Menon AU - Sheryl S. Moy AU - Stephanie L. Gupton TI - Mammalian TRIM67 Functions in Brain Development and Behavior AID - 10.1523/ENEURO.0186-18.2018 DP - 2018 May 01 TA - eneuro PG - ENEURO.0186-18.2018 VI - 5 IP - 3 4099 - http://www.eneuro.org/content/5/3/ENEURO.0186-18.2018.short 4100 - http://www.eneuro.org/content/5/3/ENEURO.0186-18.2018.full SO - eNeuro2018 May 01; 5 AB - Class I members of the tripartite motif (TRIM) family of E3 ubiquitin ligases evolutionarily appeared just prior to the advent of neuronal like cells and have been implicated in neuronal development from invertebrates to mammals. The single Class I TRIM in Drosophila melanogaster and Caenorhabditis elegans and the mammalian Class I TRIM9 regulate axon branching and guidance in response to the guidance cue netrin, whereas mammalian TRIM46 establishes the axon initial segment. In humans, mutations in TRIM1 and TRIM18 are implicated in Opitz Syndrome, characterized by midline defects and often intellectual disability. We find that although TRIM67 is the least studied vertebrate Class I TRIM, it is the most evolutionarily conserved. Here we show that mammalian TRIM67 interacts with both its closest paralog TRIM9 and the netrin receptor DCC and is differentially enriched in specific brain regions during development and adulthood. We describe the anatomical and behavioral consequences of deletion of murine Trim67. While viable, mice lacking Trim67 exhibit abnormal anatomy of specific brain regions, including hypotrophy of the hippocampus, striatum, amygdala, and thalamus, and thinning of forebrain commissures. Additionally, Trim67−/− mice display impairments in spatial memory, cognitive flexibility, social novelty preference, muscle function, and sensorimotor gating, whereas several other behaviors remain intact. This study demonstrates the necessity for TRIM67 in appropriate brain development and behavior.