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Mid1 deletion leads to cognitive dysfunction in Opitz syndrome by regulates neural rhythms through the inhibition of p-Creb by PP2Ac

Yang, Z.; Li, P.; Chen, Y.; Guo, X.; Liu, P.; Ni, G.; Liu, S.; Chen, L.; Ming, D.

2024-10-09 neuroscience
10.1101/2024.10.09.617363 bioRxiv
Show abstract

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 of MID1 gene 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 of MID1 has been studied for many years, the effect and mechanism of complete deletion of MID1 gene on OS nervous system still need to be further explored. Here we find that Mid1 gene is necessary for the normal development of hippocampus (HPC), and Mid1 gene knockout (Mid1-/y) mice showed a significant decrease in rhythm in HPC and abnormal synchronization of {gamma} rhythm in prefrontal cortex and hippocampus (PFC-HPC), showing decreased synaptic plasticity and learning and memory dysfunction.

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