Mid1deletion leads to cognitive dysfunction in Opitz syndrome by regulates neural rhythms through the inhibition of p-Creb by PP2Ac

MID1 is an E3 ubiquitin ligase of the tripartite motif (TRIM) subfamily of RING-containing protein¹. MID1 is involved in many basic biological processes, especially during embryonic development. Mutation, truncation or complete deletion ofMID1gene is the cause of Opitz G/BBB syndrome (OS). OS is a rare genetic disease of nervous system, which is characterized by midline structural development defects during embryogenesis, including structural brain abnormalities, developmental retardation and mental retardation². Although the function ofMID1has been studied for many years, the effect and mechanism of complete deletion ofMID1gene on OS nervous system still need to be further explored. Here we find thatMid1gene is necessary for the normal development of hippocampus (HPC), andMid1gene knockout (Mid1^-/y) mice showed a significant decrease in α rhythm in HPC and abnormal synchronization of γ rhythm in prefrontal cortex and hippocampus (PFC-HPC), showing decreased synaptic plasticity and learning and memory dysfunction.